Phase benzyltriethylammonium

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 highest yields in the Ciamician-Dennstedt reaction have been achieved using phase transfer catalysts (Table 8.3.1). In the reaction, the pyrrole or indole and a phase transfer catalyst (PTC, in this case benzyltriethylammonium chloride) are dissolved in chloroform and aqueous sodium hydroxide is added. Yields are typically in the 40s to 60s (rather than in the 20s for a typical Ciamician-Dennstedt reaction). More recently, yields as high as 80% have been reported using tetra-n-butylammonium hydrogen sulphate as the phase transfer catalyst. ... 

In the condensation reaction between chloro- and bromo-methyl aryl sulfones and carbonyl compounds, a-sulfonyloxiranes were obtained. In this condensation reaction, bases such as potassium t-butoxides372, NaH373 and aqueous concentrated hydroxide with benzyltriethylammonium chloride under two-phase condensation were used374. In the reaction with aldehydes only the trans-epoxide isomers resulted, whereas lith-iofluoromethyl phenyl sulfone 289375 and 291376 were found to add to aldehydes affording /J-hydroxysulfones 290 and 292, respectively. 

For example, direct treatment of red phosphorus with potassium hydroxide in a mixture of dioxane and water with a phase-transfer catalyst (benzyltriethylammonium chloride) allows direct reaction with primary haloalkanes to form the trialkylphosphine oxide in moderate (60-65%) yield.1415 Allylic and benzylic halides are similarly reported to generate the corresponding tertiary phosphine oxides. When the reaction is performed with a,(o-dihalides, cyclic products are generated only with four- and five-carbon chains the third site... 

The following quaternary ammonium salts are used as phase transfer catalyst tetra-K-butylammonium chloride (TBAC), tetra-n-butylammonium bromide (TBAB), benzyltriethylammonium chloride (BTEAC), and benzyltriethylammo-nium bromide (BTEAB). Chlorinated hydrocarbons, such as dichloromethane (DCM), chloroform (CF), tetrachloromethane (TCM), 1,2-dichloromethane (DCE), and nitrobenzene (NB) are used as solvents. The effects of phase-transfer catalyst and solvent on the yield and reduced viscosity are summarized in Table 9.1. 

It is worth mentioning at this point that according to Normant et al. (1975) simple polyamines such as tetramethylethylenediamine (TMEDA) are even more active than [2.2.2]-cryptand in the benzylation of acetates in acetonitrile under liquid-solid conditions. These authors suggested that the activity was due to salt solubilization by cation complexation and not to formation of a quaternary ammonium ion since the latter showed no activity. This statement, however, is not in line with the results of Cote and Bauer (1977), who were unable to detect any interaction between K+ and TMEDA in acetonitrile. Furthermore, Vander Zwan and Hartner (1978) found Aliquat 336 (tricaprylylmethylammonium chloride) to be almost as effective as TMEDA in this reaction (Table 30). It might well be, however, that in amine-catalysed benzylation reactions the quaternary salt formed in situ acts both as a reactant and as a phase-transfer catalyst, since Dou et al. (1977) have shown that the benzyltriethylammonium ion is a powerful benzylation agent. 

The preparation of phosphoramidates from dialkyl phosphites, using the Todd-Atherton procedure, has been carried out in two-phase systems containing a phase-transfer agent, for example benzyltriethylammonium chloride, at 5 mole % concentration.84... 

A -(4-Toluenesulphonyl)sulphilimines, which are useful precursors in the synthesis of oxiranes and in alkylidene transfer reactions, have been prepared under solidiliquid phase-transfer catalytic conditions from Chloramine-T [2], Comparable yields are obtained irrespective of whether the reaction is catalysed by Adogen or by benzyltriethylammonium chloride (Table 4.31). The procedure is an improvement on the liquiddiquid two-phase method [3]. 

It is noteworthy that benzyltriethylammonium chloride is a slightly better catalyst than the more lipophilic Aliquat or tetra-n-butylammonium salts (Table 5.2). These observations obviously point to a mechanism in which deprotonation of the amine is not a key catalysed step. As an extension of the known ability of quaternary ammonium halides to form complex ion-pairs with halogen acids in dichloromethane [8], it has been proposed that a hydrogen-bonded ion-pair is formed between the catalyst and the amine of the type [Q+X—H-NRAr] [5]. Subsequent alkylation of this ion-pair, followed by release of the cationic alkylated species, ArRR NH4, from the ion-pair and its deprotonation at the phase boundary is compatible with all of the observed facts. 

Alkylation of the more acidic hydrazo [25] and triazene [26] systems proceeds readily under liquiddiquid two-phase conditions, using tetra-n-butylammonium hydroxide and benzyltriethylammonium chloride, respectively, as the catalysts (Tables 5.5 and 5.6). 

A two-phase modification of the traditional Atherton-Todd phosphorylation reaction (Table 5.8) is aided by the addition of benzyltriethylammonium chloride [36,37]... 

The analogous reaction of benzyl and butyl naphthylcarbamates and of benzyl phenylcarbamates has been carried out in good yield under both liquiddiquid and solidrliquid two-phase conditions, using benzyltriethylammonium chloride as the catalyst [16, 17]. A similarly catalysed /V-alkylation of the ethyl carbamic esters derived from 1,2-diaminobenzene is reported [17] to lead to the formation of 1,3-dialkylbenzimidazol-3-ones (Scheme 5.7). 

In contrast, liquidiliquid phase-transfer catalysis is virtually ineffective for the conversion of a-bromoacetamides into aziridones (a-lactams). Maximum yields of only 17-23% have been reported [31, 32], using tetra-n-butylammonium hydrogen sulphate or benzyltriethylammonium bromide over a reaction time of 4-6 days. It is significant that a solidiliquid two-phase system, using solid potassium hydroxide in the presence of 18-crown-6 produces the aziridones in 50-94% yield [33], but there are no reports of the corresponding quaternary ammonium ion catalysed reaction. Under the liquidiliquid two-phase conditions, the major product of the reaction is the piperazine-2,5-dione, resulting from dimerization of the bromoacetamide [34, 38]. However, only moderate yields are isolated and a polymer-supported catalyst appears to provide the best results [34, 38], Significant side reactions result from nucleophilic displacement by the aqueous base to produce hydroxyamides and ethers. 

It can be assumed that the azoles are deprotonated by the interfacial exchange mechanism, but it is noteworthy that it has been suggested that the rate of alkylation of indole under liquiddiquid two-phase conditions decreases with an increase in the concentration of the sodium hydroxide [8]. The choice of catalyst appears to have little effect on the reaction rate or on the overall yields of alkylated azole. Benzyltriethylammonium chloride, Aliquat, and tetra-n-butylammonium hydrogen sulphate or bromide have all been used at ca. 1-10% molar equivalents (relative to the concentration of the azole) for alkylation reactions, but N-arylation of indole with an activated aryl halide requires a stoichiometric amount of the catalyst [8]. 

V-(p-Toluenesulphonyl)sulphilimines have been prepared under solidtliquid phase-transfer catalytic conditions from the reaction of sulphides with Chloramine-T [25] (see Section 4.5). Osmium-catalysed oxyamination of alkenes by Chloramine-T under two-phase conditions is aided by the addition of benzyltriethylammonium chloride. p-Aminoalkanols are obtained in good yields (60-75%) [26]. 

Organoboranes react with ethyl 4-nitrobenzenesulphonyloxycarbamate under basic two-phase conditions in the presence of benzyltriethylammonium chloride or Aliquat to yield ethyl (V-alkylcarbamates [38]. The reaction probably proceeds via the initial formation of the nitrene, which reacts with the borane to form a B -N+ zwitterion. Subsequent rearrangement and solvolysis leads to the product. Aliquat is the better catalyst for the higher-molecular-weight boranes. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

As indicated in Chapter 1, the hydroxide ion is not readily transported into the organic phase, particularly when the benzyltriethylammonium ion is employed as the catalytic cation. Hence, the reaction of chloroform with the hydroxide ion must occur by an interfacial mechanism. The interfacial reaction initially produces the trichloromethyl anion, which immediately forms an effective ion-pair with the benzyltriethylammonium cation. Diffusion of the ion-pair into the bulk of the organic phase occurs, followed by a slow decomposition of the trichloromethyl anion... 

Benzyltriethylammonium chloride is frequently used as the phase-transfer catalyst, but it has been noted that the catalyst itself produces phenylacetic acid under the carbonylation conditions [6]. Trimethyl(phenyl)ammonium chloride and tetra-n-butylammonium chloride both catalyse the reaction efficiently. 

A study of Hofmann vs Saytzeff elimination from 2-bromooctane under soliddiquid two-phase conditions [6] shows that the 1-octene 2-octene ratio depends not only on the base used, but also on the catalyst. Aliquat is the most effective catalyst giving a 98% overall yield with a l-octene 2-octene ratio of ca. 2 1. Benzyltriethylammonium chloride catalyses a 95% conversion with a ratio of ca. 3 1 in favour of the 1-octene. Potassium hydroxide and potassium t-butoxide favour the formation of 1-octene, whereas sodium methoxide and sodium ethoxide favour the formation of 2-octene [6]. 

Primary and secondary alcohols are oxidized slowly at low temperatures by benzyltriethylammonium permanganate in dichloromethane primary alcohols produce methylene esters (60-70%), resulting from reaction of the initially formed carboxylate anion with the solvent, with minor amounts of the chloromethyl esters and the carboxylic acids. Secondary alcohols are oxidized (75-95%) to ketones [34] the yields compare favourably with those obtained using potassium permanganate on a solid support. 1,5-Diols are oxidized by potassium permanganate under phase-transfer catalytic conditions to yield 8,8-disubstituted-8-valerolactones [35] (Scheme 10.1). 

Many examples of the phase-transfer catalysed epoxidation of a,(3-unsaturated carbonyl compounds using sodium hypochlorite have been reported [e.g. 7-10]. The addition of transition metal complexes also aids the reaction [11], but advantages in reaction time or yields are relatively insignificant, whereas the use of hexaethyl-guanidinium chloride, instead of a tetra-alkylammonium salt, enhances the rate of epoxidation while retaining the high yields (>95%) [10]. Intermediate (3-haloalkanols are readily converted into the oxiranes under basic conditions in the presence of benzyltriethylammonium chloride [12]. 

Quaternary ammonium periodates, prepared either from periodic acid and the quaternary ammonium hydroxide [21, 22] or by metathesis from sodium periodate and a quaternary ammonium salt [e.g. 23-25], have been used for a range of oxidations at stoichiometric levels in two-phase systems [21-33], The tetra-n-butyl-ammonium and hexadecyltrimethylammonium salts are both highly soluble in organic solvents (considerably less so in water), whereas benzyltriethylammonium periodate has a lower solubility and stability than either salt. 

An intriguing use of a quaternary ammonium salt in a two-phase reaction is to be found with the regeneration of 1 -benzyl-1,4-dihydronicotinamide by sodium dithionite in a biomimetic reduction of thiones to thiols [12], The use of sodium dithionite in the presence of sodium carbonate for the 1,4-reduction of the pyri-dinium salts to 1,4-dihydropyridines is well established but, as both the dithionite and the pyridinium salts are soluble in water and the dihydropyridine and the thione are insoluble in the aqueous phase and totally soluble in the organic phase, it is difficult to identify the role of the quaternary ammonium salt in the reduction cycle. It is clear, however, that in the presence of benzyltriethylammonium chloride, the pyridine system is involved in as many as ten reduction cycles during the complete conversion of the thione into the thiol. In the absence of the catalyst, the thione is recovered quantitatively from the reaction mixture. As yet, the procedure does not appear to have any synthetic utility. 

Hydride ion transfer from formic acid and its salts finds widespread application in the reduction of organic substrates, but limited use has been made of the procedure under phase-transfer catalytic conditions. However in the presence of a ruthenium complex catalyst, it is possible to selectively reduce the C=C bonds of conjugated ketones with sodium formate [11], The rate of reduction is fastest with tetrahexyl-ammonium hydrogensulphate and Aliquat the complete reduction of chalcone being effected within one hour, whereas with benzyltriethylammonium chloride only ca. 15% reduction is observed after two hours under similar conditions. 

Complexes of other metals are also capable of catalyzing useful carbonylation reactions under phase transfer conditions. For example, certain palladium(o) catalysts, like Co2(C0)g, can catalyze the carbonylation of benzylic halides to carboxylic acids. When applied to vinylic dibromides, unsaturated diacids or diynes were obtained, using Pd(diphos)2[diphos l,2-bis(diphenylphosphino)ethane] as the metal catalyst, benzyltriethylammonium chloride as the phase transfer agent, and t-amyl alcohol or benzene as the organic phase(18),... 

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. 

Ethyl N-alkylcarbamates via hydroboratitm. The reaction of trialkylboranes with carboethoxynitrene is best conducted under phase-transfer conditions (equation I). Either benzyltriethylammonium chloride or methyl trioclylammonium chloride is a satisfactory catalyst.2... 

Isomerization of allylic alcoholsAllylic alcohols can be isomerized to carbonyl compounds by several organometallic reagents at elevated temperatures. The reaction can be conducted at 25-30° overnight with [Rh(CO)2Cll2 under phase-transfer conditions. Cleaner reactions obtain if benzyltriethylammonium chloride is used as catalyst. 

Benzoin condensation.1 The benzoates of cyanohydrins of aromatic aldehydes undergo benzoin condensation with an aromatic aldehyde in 50% NaOH/C6H6 in the presence of a phase-transfer catalyst, benzyltriethylammonium chloride. Theoretically two symmetrical and two unsymmetrical benzoins are possible, but in practice only one unsymmetrical benzoin is formed, that in which the carbonyl group is adjacent to the benzene ring substituted by the more electron-donating group. 

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