Direct Quaternary Ammonium Compounds

Quaternary ammonium compounds as structure directing agents in zeolite synthesis... 

Paraquat (1,1 dimethyl, 4,4 bipyridyl) is a nonselective contact herbicide. It is used almost exclusively as a dichloride salt and usually is formulated to contain surfactants. Both its herbicidal and toxicological properties are dependent on the ability of the parent cation to undergo a single electron addition, to form a free radical that reacts with molecular oxygen to reform the cation and concomitantly produce a superoxide anion. This oxygen radical may directly or indirectly cause cell death. Diquat, l,T-ethylene-2,2 -dipyridylium, is a charged quaternary ammonium compound often found as the dibromide salt. The structure of diquat dibromide and that of the closely related herbicide paraquat can be seen in Fig. 4.5. 

Acetylcholinesterase can be inhibited by two general mechanisms. In the first mechanism, positively charged quaternary ammonium compounds bind to the anionic site and prevent ACh from binding—a simple competitive inhibition. In the second mechanism, the agents act either as a false substrate for the cholinesterase or directly attack the esteratic site in both cases they covalently modify the esteratic site and non-competitively prevent further hydrolytic activity. Either mechanism can be effective in preventing the hydroly-... 

Hyoscine butylbromide, an antimuscarinic antispasmodic, is a hydrophilic quaternary ammonium compound that is poorly absorbed from the gut and claimed to act directly on it, and any drug absorbed does not readily cross the blood-brain barrier. Nevertheless, antimuscarinic side-effects have been very occasionally reported. Hyoscine butylbromide is contraindicated in patients with glaucoma, and caution is advised for men with prostate problems, the elderly and pregnant women. 

Clidinium bromide, another quaternary ammonium compound with antimuscarinic activity, is used in a fixed combination with chlordiazepoxide hydrochloride (2.5 mg of clidinium and 5 mg of chlordiazepoxide Librax) however, such combinations are of limited value in patients with IBS because of the risk of habituation and rebound withdrawal. Cimetropium is another antimuscarinic compound that reportedly is effective in patients with IBS. Otilonium bromide has been used extensively for patients with IBS in other parts of the world. It is an ammonium salt with antimuscarinic effects that also appears to block Ca + channels and neurokinin NK-2 receptors. Mebeverine hydrochloride is a derivative of hydroxybenzamide that appears to have a direct effect on the smooth-muscle cell, blocking K+ and Ca channels. It is widely used outside of the United States as an antispasmodic agent for patients with IBS. 

Direct replacement of an amino group by hydrogen is possible only in certain cases. Such reductive fissions are particularly well known for tertiary amines and quaternary ammonium compounds and occur especially readily with allyl- and benzyl-substituted amines. In the last-mentioned cases the benzyl group is removed as toluene, and this reaction route is used for preparation of secondary from primary aliphatic amines the primary amine is first condensed with benzaldehyde, and the resulting Schiff base is reduced to the alkylbenzylamine this is converted by alkylation into the dialkylbenzyl-amine, from which finally the benzyl group is removed by catalytic hydrogenation 544... 

Weiss, C. S., Hazlett, J. S., Datta, M. H., and Danzer, M. H., Determination of quaternary ammonium compounds by capillary electrophoresis using direct and indirect UV detection, J. Chromatogr., 608, 325-332, 1992. 

The effect of pH changes on the potency of local anesthetics has been extensively investigated (30). Based on these studies, it was concluded that local anesthetics block the action potential by first penetrating the nerve membrane in their un-ionized forms and then binding to a site within the channels in their onium forms. Perhaps the most direct support for this hypothesis comes from the experimental results of Narahashi et al. (31,32), who studied the effects of internal and external perfusion of local anesthetics (both tertiary amines and quaternary ammonium compounds), at different pH values, on the sodium conductance of the squid axon. The observation that both tertiary amines and quaternary ammonium compounds produce greater nerve blockage when applied internally indicates an axoplasmic site for these compounds. 

ESD are commonly referred to as antistats or antistatic surfactants , and are mostly low molecular weight ethoxylated amines, quaternary ammonium compounds, phosphates (organic) and PEG esters, ethoxylated esters, and others. They are usually applied in quite large quantities (2% or more), either by compounding directly with the plastics and... 

Basic carriers (Table 27.1) consist mainly of amine-based compounds such as quaternary ammonium salts (e.g., Aliquat 336), tertiary amines (e.g., tri-n-octylamine [TOA], tri-isooctylamine [TlOA]), weakly basic compounds (e.g., alkyl derivatives of pyridine N oxides), and thiadiazine derivatives (e.g., 5-(4-phenoxyphenyl)-6/f-l,3,4-thiadiazin-2-amine [FFAT]). The reason for this classification is related to the similarity in the extraction mechanism involving the carriers discussed. In the case of fully substituted quaternary ammonium compounds (e.g., Aliquat 336), the carrier reacts as an anion exchanger forming an ion-pair with another anion from the feed phase, which can be a complex metal anion. In the case of amine and other weak bases mentioned earlier, the carrier must be protonated first in order to allow anion exchange with another anion from the feed phase or with a complex metal anion. Alternatively, the carrier may react directly with a protonated complex metal anion [16]. 

Although the applications described here have concerned diverse macromolecular samples, pyrolysis is also of utility in the analysis of smaller molecules, particularly quaternary ammonium compounds, which undergo quantitative thermal fragmentation to volatile products. For example, the specificity and sensitivity afforded by Py-GC/MS with mass fragmentography renders the technique suitable for the analysis of endogenous neurotransmitters such as acetylcholine at the l-2pmol level. However, in all cases, analytical throughput is limited by the retention times of the pyrolysis products, a condition that is particularly severe in taxonomic applications. Automation allows extended use, but direct Py-MS... 

Salts of weak acids such as carboxylates , picrates , or carbonates can be titrated with mineral acids. Ammonium halides can be converted into acetates by treatment with mercury(n) acetate in glacial acetic acid, and determined by subsequent titration with perchloric acid . Salts of strong acids, such as sulphates and halides, can be determined by measuring the anion, or alternatively the quaternary cation can react to form complexes which precipitate, or remain in aqueous solution, or have to be extracted into oi nic solvents. These complexes can be measured directly, or indirectly by measuring the excess reagent. In Table 13 appears a list of reagents used for the determination of quaternary ammonium compounds by complex formation. 

One final note regarding the use of crown ethers as phase transfer catalysts there is little literature which directly compares quaternary ammonium catalysts with crown ethers in liquid-liquid processes (see Sect. 1.10) [48]. There are examples where both have been tried and are effective. In general, however, it appears that for solid-liquid phase transfer processes, the crowns are far better catalysts than are the quaternary ammonium ions. In order for a solid-liquid phase transfer process to succeed, the catalyst must remove an ion pair from a solid matrix. The quaternary catalysts have no chelating heteroatoms with available lone pairs which would favor such a process. The combination of a quaternary catalyst and some simple coordinating amine or ether would probably succeed [28, 32, 34]. It seems likely, as mentioned above, that it is the combination of diamine and quaternary catalyst generated in situ which accounts for the success of Normanf s catalysts [28]. It is interesting to speculate on the possibility of using a quaternary ammonium compound and a drop of water as a catalytic system. 

Hennis and coworkers reported that the reaction of carboxylates with alkyl chlorides is catalyzed by tertiary amines, the combination of tertiary amines and sodium iodide or quaternary ammonium compounds [3, 4]. It was found that the ester formation was catalyzed by quaternary ammonium salts and that these were generated in situ from the amine and alkyl halide. Sodium iodide in 2-butanone converted the alkyl chloride to the more reactive iodide (the Finkelstein reaction) which in turn alkylated amine. Alkyl iodides added directly to the reaction mixture were even more active co-catalysts but the preformed quaternary ammonium salt was the most effective catalyst. It was suggested that the enhanced solubility of the quaternary ammonium carboxylate or the lack of tight ion pairing in this salt might account for the... 

Street, Kenyon, and Watson (87) reported that the estimation of free choline in plant tissues by the oxidation of choline to trimethylamine (50,51) could not be conducted directly on the tissue. It was necessary first to extract plant tissues with cold toluene saturated with water or with 80% ethanol this was followed by precipitation of choline as the reineckate at pH 5-6. Neuiine and carnitine were assumed to be absent in plant tissues, but acetylcholine and other quaternary ammonium compounds would be expected to interfere in the analysis of choline by this method. 

Sommer has described a general exhaustive alkylation procedure for the direct synthesis of quaternary ammonium compounds. As protonation of sterically hindered amines is only slightly affected hysteric hindrance, whereas kinetic nucleophilicity is greatly decreased, the use of a sterically hindered base of greater base strength than the substrate amine will bind up the acid generated on alkylation this system allows quaternization under mild conditions, with the minimum of manipulation. 

Grit, M. Hair dye composition comprising direct dyes, quaternary ammonium compounds, and... 

Metcalfe, L. D., Direct GC analysis of long chain quaternary ammonium compounds, J. Am. Oil Chem. Soc., 1963,40,25-27. 

Prior to the availability of straight-chain, petroleum-based surfactants, the sole sources of raw materials for cationic surfactants were vegetable oils and animal fats. All those materials could be considered to be derivatives of fatty amines of one, two, or three alkyl chains bonded directly or indirectly to a cationic nitrogen group. The most important classes of these cationics are the simple amine salts, quaternary ammonium compounds, and amine oxides ... 

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