Catalysts quaternary ions

Both of the above-mentioned catalyst types get the anions into the organic phase, but there is another factor as well. There is evidence that sodium and potassium salts of many anions, even if they could be dissolved in organic solvents, would undergo reactions very slowly (dipolar aprotic solvents are exceptions) because in these solvents the anions exist as ion pairs with Na or and are not free to attack the substrate (p. 443). Fortunately, ion pairing is usually much less with the quaternary ions and with the positive cryptate ions, so the anions in these cases are quite free to attack. Such anions are sometimes referred to as naked anions. 

Addition of water (36) or alcohols (37—39) direcdy to butadiene at 40—100°C produces the corresponding unsaturated alcohols or ethers. Acidic ion exchangers have been used to catalyze these reactions. The yields for these latter reactions are generally very low because of unfavorable thermodynamics. At 50°C addition of acetic acid to butadiene produces the expected butenyl acetate with 60—100% selectivity at butadiene conversions of 50%. The catalysts are ion-exchange resins modified with quaternary ammonium, quaternary phosphonium, and ammonium substituted ferrocenyl ions (40). Addition of amines yields unsaturated alkyl amines. The reaction can be catalyzed by homogeneous catalysts such as Rh[P(C(5H5)3]3Q (41) or heterogeneous catalysts such as MgO and other solid bases (42). 

Transition metal oxidants such as permanganate, ruthenium tetroxide and diromium(VI) oxide are convenient and efficient reagents for routine cleavage reactions. The use of phase transfer catalysts (quaternary ammonium and phosphonium ions, primarily) has made it possible to solubilize transition metal oxides such as permanganate and chromatt in nonaqueous solvents, and to therdry increase the scope of these reactions substantially. ... 

In a PTC reaction catalyzed by quaternary onium salt involving the extraction of catalyst-anion ion pair, the kinetics is complicated by the reactive form of the reactant anion in the organic phase. From both physical and kinetic points of view, two types of ion pairs can be considered to exist, namely, the loose or solvent separated ion pairs and the tight or contact ion pairs. Since any form of the anion (free ion, catalyst-anion ion pair, or ion aggregates) could be the reactive species in the PTC reactions, it is worthwhile exploring the kinetics associated with the following two limiting cases of the reactive form of the anion. 

It is interesting to note that the very widely used Makosza catalyst , benzyl triethyl ammonium chloride, does not show high efficiency in this study. 4) Phosphonium ions are somewhat more effective and thermally stable than the corresponding ammonium catalysts and both are better than arsonium systems. 5) Substitution of the quaternary ion by alkyl rather than aryl groups yields more effective catalysts. 6) Reaction rates are generally greater in orf/io-dichlorobenzene (and presumably in other chlorocarbon media) than in benzene, and botli are better than heptane. In connection with this latter point, Ugelstad and coworkers have studied the reactions of quaternary ammonium phenoxide ions with alkyl halides in a variety of media and concluded that the... 

One fact about the use of quaternary ions as phase transfer catalysts should be noted. In general, the large, lipophilic quaternary ions are soft in the HSAB sense [25]. As a consequence, the quat tends to pair with the softest anion available in solution. If both iodide ions and hydroxide ions were present, for example, the quat would pair with iodide. If reaction with hydroxide was desired, the catalyst would be poisoned by the presence of iodide. The source of an ion such as iodide could be from the catalyst originally added or it could be the leaving group in the substitution reaction. The choice of reaction conditions should therefore include a consideration of cation, anion, nucleophile and nucleofuge. 

Most of Normant s catalysts are 1,2-diamines [28]. The early work of Jarrousse [2] involved not only a quaternary ion but a l-amino-2-ether system which could coordinate cations just as the diamines do. Both the coordination effect and quaternary ion effect may be operative in that early example and also in Normant s work. Moreover, the phosphonate catalysts recently developed by Mikolajczky and coworkers [32], as a result of their earlier finding that Wittig-Homer-Emmons reactions require no additional catalyst [33], all contain two potential coordination sites. The combination of coordination properties and nucleophilic nitrogen is quite apparent in the so-called polypode ligands developed by Montanari [34]. 

Phase transfer processes rely on the catalytic effect of quaternary onium or crown type compounds to solubilize in organic solutions otherwise insoluble anionic nucleophiles and bases. The solubility of the ion pairs depends on lipophilic solvation of the ammonium or phosphonium cations or crown ether complexes and the associated anions (except for small amounts of water) are relatively less solvated. Because the anions are remote from the cationic charge and are relatively solvation free they are quite reactive. Their increased reactivity and solubility in nonpolar media allows numerous reactions to be conducted in organic solvents at or near room temperature. Both liquid-liquid and solid-liquid phase transfer processes are known the former ordinarily utilize quaternary ion catalysts whereas the latter have ordinarily utilized crowns or cryptates. Crowns and cryptates can be used in liquid-liquid processes, but fewer successful examples of quaternary ion catalysis of solid-liquid processes are available. In most of the cases where amines are reported to catalyze phase transfer reactions, in situ quat formation has either been demonstrated or can be presumed. 

Makosza has argued that the proton transfer occurs at the interface, and that the remainder of the reaction sequence occurs in the bulk organic phase [9]. He has drawn attention to the following facts. First, hydroxide is a harder ion than either trichloromethide or chloride and the latter two would tend to pair with the soft quaternary ion rather than the former. As a consequence, the base concentration in the organic phase should be low. In addition, numerous examples of isotopic (C-D for C-H) exchange are known for weak carbon acids. These exchange reactions are frequently accomplished under biphasic conditions in the absence of a phase transfer catalyst. Finally, the observation that tertiary amines are effective catalysts for the dichlorocarbene... 

Alkyl iodides are less satisfactory in this reaction than are the chlorides for two reasons. First, the iodides are generally more expensive than the corresponding chlorides. Second, iodide ion tends to poison the phase transfer catalysts. Iodide ion preferentially pairs with quaternary alkylammonium ion in nonpolar solution. As a result, exchange to form the quaternary ammonium alkoxide which would... 

Phenols have been phosphorylated under phase transfer conditions in the presence of a nucleophilic catalyst [31, 32]. The reaction of 4-nitrophenol with dimeth-oxythiophosphoryl chloride is ordinarily slow and leads to a mixture of the desired methyl parathion and hydrolysis products. Addition of N-methylimidazole enhanced the rate but the best results were obtained when both the imidazole and a quaternary ammonium salt (TBAB) were used at the same time. The co-catalysis was accounted for in terms of nucleophilic activation of the acylating agent by imidazole and solubilization of the phenoxide by ion pairing with the quaternary ion. The overall transformation is formulated in equation 6.13. 

Crown ethers have also been utilized as phase transfer catalysts in solid-liquid phase transfer cyanide displacements. These reactions are generally carried out in methylene chloride or acetonitrile solution with 18-crown-6 as catalyst and solid potassium cyanide as nucleophile source [5, 6]. Small amounts of water are found not to affect the course of the reaction [5], suggesting some hydration of cyanide ion under these conditions. This is not surprising inasmuch as Starks reported that in the liquid-liquid phase transfer process, four to five molecules of water apparently accompanied each nucleophile into nonpolar solution [2]. It seems likely that if water were or could be rigorously excluded, (i.e., naked anions obtained), the reactivity of cyanide would be even higher. Despite the apparent similarity of the solid-liquid and liquid-liquid phase transfer processes, it should be noted that qualitative differences in the relative reactivity of primary alkyl halides (R—Cl vs. R—Br) have been observed for the crown and quaternary ion cases [2, 6]. Specifically, Starks found that for the reaction of cyanide ion with A2-octyl halides, methanesulfonate... 

All four commonly occurring halide ions (fluoride [1-5], chloride [5—11], bromide [5, 8-10], and iodide [5, 7-9, 10, 12-15] have been phase-transferred and in the process, quaternary ions [1, 6-8, 10, 12-15], crowns [2, 4, 8, 9, 13], cryptates [3, 13] and resins [5] have all been utilized. Most of the processes reported are essentially Finkelstein reactions [16]. In a typical phase transfer of fluoride utilizing crown ether as catalyst, an acetonitrile solution of benzyl bromide is stirred with a catalytic amount of 18-crown-6 and solid potassium fluoride. The product, benzyl fluoride (see Eq. 9.1), is isolated in quantitative yield [2]. 

The crown ether catalyzed phase transfer reductions which have been reported are similar to the quaternary ion catalyzed reactions in the sense that if the proper catalyst is chosen the reactions yield well but appear to offer no special advantage over more traditional reduction methodology. The dibenzo-18-crown-6 catalyzed sodium borohydride reduction of several ketones in boiling toluene (5 h reaction time) has been reported [7]. By this method, acetophenone, cyclohexanone and 2-heptanone were reduced in 49%, 50% and 41% yields respectively. 

Pierre and Handel have studied the effect of [2.1.1]-cryptate on the lithium aluminum hydride reduction of cyclohexanone in diglyme [16]. The [2.1.1]-cryptate strongly complexes lithium ion and if sufficient cryptate is used to sequester all of the lithium ion, no reduction occurs. Apparently, lithium ion is needed as an electrophilic catalyst for the reduction to occur (see Eq. 12.8). Consistent with this interpretation is the observation that even in the presence of cryptate, reduction will occur if an excess of lithium iodide is also present. The relatively low reactivity of tetrabutyl-ammonium borohydride in benzene solution may also reflect this property, at least in part [9]. Likewise, the jS-hydroxyethyl quaternary ammonium ions may be better catalysts than non-oxygenated quaternary ions because the hydroxyl may hydrogen bond to carbonyl and provide electrophilic catalysis [5]. Similar, though less dramatic results, have been observed in the reduction of aromatic aldehydes and ketones by lithium aluminum hydride in the presence of [2.1.1]-cryptate [17]. 

If the substrate is an alcohol, some dialkyl ethers can be synthesized in a two-phase version of the Williamson synthesis, and thioethers or dithioacetals result from alkylation of thiols, with alkyl halides or CH2CI2 respectively, under similar conditions. The related reaction of equation (2) has been used to make an evaluation of several catalysts, and it has been found that the larger, more symmetrical, quaternary ions are the most efficient. 

Amines as Catalysts. Some reports have appeared on the use of amines as catalysts in PTC nucleophilic substitution methods. For example, the preparation of alkyl thiocyanates or nitriles from alkyl bromides in two-phase systems may be assisted by a variety of primary, secondary, or tertiary amines as alternatives to quaternary ions. Efficient catalysis seems to require a sterically unhindered amino group with relatively high basicity (J.e. t-alkyl and aromatic amines are not fully efficient), and a total number of carbon atoms in the amine of greater than six to achieve good phase distribution of the catalysts. A similar study on the alkylation of benzyl methyl ketone reached the same conclusions, and from various observations e.g. that the reaction displayed an induction period at low catalyst concentration) it was postulated that initial alkylation of the amine by the alkylating agent (usually a halide) was essential to provide quaternary ions as the actual catalyst,... 

Nucleophilic Substitutions.—Many of the nucleophilic substitutions covered by equation (1) can be catalysed as effectively in liquid-liquid two-phase systems by crown and cryptand compounds as by quaternary ions. Alkyl substitution on the basic crown skeleton of (28), as in (31), was found to increase the efficiency of catalysis for the conversion of alkyl mesylates to halides, presumably by ensuring partitioning of the crown-salt complex between the phases. A similar observation has been made using alkyl-substituted crown (32) and aza-crown compounds (33) as catalysts in two-phase reactions, for example between iodide, cyanide or thiocyanate aniohs and an alkyl bromide. Alkyl substitution in the macrobicyclic cryptands (34) has the same effect on Sn processes, and in all the above cases systems can be devised with catalytic efficiency comparable to or greater than that achieved by quaternary ion PTC. 

Chiral onium salts, such as chiral quaternary ammonium and phosphonium salts, are the predominant choice for asymmetric PTC. The onium salt-triggered PTC is beheved to proceed via the formation of catalyst-substrate ion pairs. High enantioselectivity could be achieved if the chiral cation was designed with effective structural features. 

The nitro alcohols available in commercial quantities are manufactured by the condensation of nitroparaffins with formaldehyde [50-00-0]. These condensations are equiUbrium reactions, and potential exists for the formation of polymeric materials. Therefore, reaction conditions, eg, reaction time, temperature, mole ratio of the reactants, catalyst level, and catalyst removal, must be carefully controlled in order to obtain the desired nitro alcohol in good yield (6). Paraformaldehyde can be used in place of aqueous formaldehyde. A wide variety of basic catalysts, including amines, quaternary ammonium hydroxides, and inorganic hydroxides and carbonates, can be used. After completion of the reaction, the reaction mixture must be made acidic, either by addition of mineral acid or by removal of base by an ion-exchange resin in order to prevent reversal of the reaction during the isolation of the nitro alcohol (see Ion exchange). 

When potassium fluoride is combined with a variety of quaternary ammonium salts its reaction rate is accelerated and the overall yields of a vanety of halogen displacements are improved [57, p 112ff. Variables like catalyst type and moisture content of the alkali metal fluoride need to be optimized. In addition, the maximum yield is a function of two parallel reactions direct fluorination and catalyst decomposition due to its low thermal stability in the presence of fluoride ion [5,8, 59, 60] One example is trimethylsilyl fluoride, which can be prepared from the chloride by using either 18-crown-6 (Procedure 3, p 192) or Aliquot 336 in wet chlorobenzene, as illustrated in equation 35 [61],... 

It is important to make the distinction between the multiphasic catalysis concept and transfer-assisted organometallic reactions or phase-transfer catalysis (PTC). In this latter approach, a catalytic amount of quaternary ammonium salt [Q] [X] is present in an aqueous phase. The catalyst s lipophilic cation [Q] transports the reactant s anion [Y] to the organic phase, as an ion-pair, and the chemical reaction occurs in the organic phase of the two-phase organic/aqueous mixture [2]. 

In some cases, the Q ions have such a low solubility in water that virtually all remain in the organic phase. ° In such cases, the exchange of ions (equilibrium 3) takes place across the interface. Still another mechanism the interfacial mechanism) can operate where OH extracts a proton from an organic substrate. In this mechanism, the OH ions remain in the aqueous phase and the substrate in the organic phase the deprotonation takes place at the interface. Thermal stability of the quaternary ammonium salt is a problem, limiting the use of some catalysts. The trialkylacyl ammonium halide 95 is thermally stable, however, even at high reaction temperatures." The use of molten quaternary ammonium salts as ionic reaction media for substitution reactions has also been reported. " " ... 

Phase transfer catalysis (PTC) refers to the transfer of ions or organic molecules between two liquid phases (usually water/organic) or a liquid and a solid phase using a catalyst as a transport shuttle. The most common system encountered is water/organic, hence the catalyst must have an appropriate hydrophilic/lipophilic balance to enable it to have compatibility with both phases. The most useful catalysts for these systems are quaternary ammonium salts. Commonly used catalysts for solid-liquid systems are crown ethers and poly glycol ethers. Starks (Figure 4.5) developed the mode of action of PTC in the 1970s. In its most simple... 

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