Deprotonation quaternary cation

Hint. Start by acetylating the pyridine to give a quaternary cationic species. How can deprotonation afford a nucleophilic enamine-like system ... 

Charles Liotta modified the Makosza interfacial mechanism. In this modification deprotonation takes place at the interfacial region and is assisted by the quaternary cation. 

Column 3 Weakly acidic cation exchanger, sodium salt. Retains quaternary cationics. Weak bases and betaines pass through. Elute with hydrochloric acid, to protonate and therefore deionise the resin. Column 4 Strongly acidic cation exchanger, free acid. Retains weak bases and betaines. Effluent contains nonionics, sulphobetaines (SS amphoterics) and phosphate triesters. Elute with ammonia, to deprotonate and deionise weak bases and to convert the betaine to the zwitterionic form. 

The effect of mixtures of surfactants and polyelectrolytes on spontaneous, water-catalysed hydrolysis (Fadnavis and Engberts, 1982) was mentioned in Section 4, but mixtures of functionalized polyelectrolytes and cationic surfacants are effective deacylating agents (Visser et al., 1983). Polymerized isocyanides were functionalized with an imidazole group and the deacylation of 2,4-dinitrophenyl acetate in the polyelectrolyte was speeded by addition of single or twin chain quaternary ammonium ion surfactants, up to a plateau value. Anionic surfactants had essentially no effect. It is probable that the cationic surfactants accelerate the reaction by increasing the deprotonation of the imidazole groups. 

The interfacial mechanism provides an acceptable explanation for the effect of the more lipophilic quaternary ammonium salts, such as tetra-n-butylammonium salts, Aliquat 336 and Adogen 464, on the majority of base-initiated nucleophilic substitution reactions which require the initial deprotonation of the substrate. Subsequent to the interfacial deprotonation of the methylene system, for example the soft quaternary ammonium cation preferentially forms a stable ion-pair with the soft carbanion, rather than with the hard hydroxide anion (Scheme 1.8). Strong evidence for the competing interface mechanism comes from the observation that, even in the absence of a catalyst, phenylacetonitrile is alkylated under two-phase conditions using concentrated sodium hydroxide [51],... 

The catalytic effect of quaternary ammonium salts in the basic liquid liquid two-phase alkylation of amines [1-3] is somewhat unexpected in view of the low acidity of most amines (pKfl>30). Aqueous sodium hydroxide is not a sufficiently strong base to deprotonate non-activated amines in aqueous solution and the hydroxide ion is not readily transferred into the organic phase to facilitate the homogeneous alkylation (see Chapter 1). Additionally, it is known that ion-pairs of quaternary ammonium cations with deprotonated amines are decomposed extremely rapidly by traces of water [4]. However, under solidrliquid two-phase conditions, the addition of a quaternary ammonium salt has been found to increase the rate of alkylation of non-activated amines by a factor of ca. 3-4 [5]. Similarly, the alkylation of aromatic amines is accelerated by the addition of the quaternary ammonium salt the reaction is accelerated even in the absence of an inorganic base, although under such conditions the amine is deactivated by the formation of the hydrohalide salt, and the rate of the reaction gradually decreases. Hence, the addition of even a weak base, such as... 

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. 

If the reaction takes place under basic conditions then the silica species are present as anions, that is, deprotonated silanol groups (Si-O-) in this case the surfactants have to be charged positively to ensure interactions between both components commonly cationic quaternary ammonium surfactants are used as the SDA this synthesis pathway is termed S+I (Fig. 3.6a). 

Nitrile-stabilized anions are so nucleophilic that they will react with alkyl halides rather well even when a crowded quaternary centre (a carbon bearing no H atoms) is being formed. In this example the strong base, sodium hydride, was used to deprotonate the branched nitrile completely and benzyl chloride was the electrophile. The greater reactivity of benzylic electrophiles compensates for the poorer leaving group. In DMF, the anion is particularly reactive because it is not solvated (DMF solvates only the Na+ cation). 

In general, methyl groups at the 4- and 5-positions of imidazole, oxazole, and thiazole do not undergo such deprotonation-mediated reactions, even when the ring is cationic. A quaternary form can be generated in situ by N-acylation (Scheme 127) <2005TL4789>. 

The parent oxacalix[3]arenes show little ability to bind alkali metals, however, a range of quaternary ammonium cations are attracted to the symmetric cavity [4]. Deprotonation of the phenol moieties allows them to bind to transition metals (scandium, titanium, vanadium, rhodium, molybdenum, gold etc.) [5-7], lanthanides (lutetium, yttrium and lanthanum) [8,9] and actinides (uranium, as uranyl)... 

Further work by Palermo and Kuroda extended the library of molecules to indude tertiary amine- and quaternary ammonium-fimctionalized methacrylates. For this series, cationic monomers were polymerized with methyl and butyl acrylate monomers. As with the styrene-based polymers of Gelman et al, the quaternary ammonium series was much less antimiaobial and somewhat less hemolytic than the primary and tertiary amine series. Again, titration of the polymers showed that there is partial deprotonation of the amine functionalities at neutral pH. The deprotonated moieties are more hydrophobic than the ammonium salts, and thus inaease the membrane activity of the polymers. No explanation was given, however, for the inaeased activity of the primary amine polymers over the tertiary amine polymers. 

Quaternary ammonium salts. Only the structure of the cation is shown. The most commonly used anions are Cl, Br, CH3COO and CH3OSO3, the last resulting from the use of dimethyl sulphate as a quaternising agent. Weak bases are shown in the deprotonated form the protonated form has the anion of whatever acid was used for protonation. 

An interesting case of catalysis by tertiary amines was reported by Isagawa and coworkers [35] (see Sect. 2.2). These investigators found that the two-phase carbene reaction originally reported almost simultaneously and independently by both Starks [36] and Makosza [11] was catalyzed not only by quaternary ammonium cations, but by amines as well. Makosza has offered an explanation of this phenomenon in terms of in situ quaternary ammonium ion formation [37]. He suggests that deprotonation of chloroform occurs at the aqueous-organic interface [38], and that the... 

Studied and to alert the reader to key problems that need to be addressed in such reactions. Three main steps are required in this process [2f] (1) deprotonation of the active methylene compound with base, which genoally occurs at the inter ce between the two layers (liquid-liquid (L/L) or solid-liquid (SifL) PTC) (2) ion-exchange of the anion (A ) with the cation of the chiral quaternary ammonium ctMnpound (quat) to form a lipt hilic ion-pair (D), which then either reacts from the interface (step 3) or is extracted into the bulk organic phase and (3) creation of the new chiral centa in product P" by all lation of the ion-pair (D) with concomitant regeneration of the catalyst. 

---