Tertiary Amines and Quaternary Ammonium Salts

One of the earliest reactions in which quaternary ammonium catalysis was recognized was in the alkylation of fatty acids with epichlorohydrin [1]. Maerker, Carmichael, and Port reported in 1961 that when stearic acid was boiled with epichlorohydrin containing benzyltrimethylammonium chloride, less than 10% ester was formed. In contrast, when the sodium salt of stearic acid was reacted under similar conditions, high yields of the glycidic ester were obtained (Eq. 6.2). In the absence of catalyst. 

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 

Carboxylate salt Alkyl halide Catalyst % Yield Ref. 

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The anion B12H11NH22 can form Schiff bases with aldehydes, which in turn can be reduced to amines, opening the way to both secondary amine derivatives of the B12H122 cluster and tertiary amines and quaternary ammonium salts after further alkylation [61]. 

RESINS (Acetal). These are thermoplastic resins, obtainable both as homopolymers and copolymers, and produced principally from formaldehyde or formaldehyde derivative. Acetal resins have the highest fatigue endurance of commercial thermoplastics. A variety of ionic initiators, such as tertiary amines and quaternary ammonium salts, are used to effect polymerization of formaldehyde. Chain transfer, shown by the following reactions, controls the molecular weight of resulting resins ... 

Sn2 conditions problem with multiple alkylation acceptable yields for tertiary amines and quaternary ammonium salts... 

The reaction between alkyl hahdes and ammonia or primary amines is not usually a feasible method for the preparation of primary or secondary amines, since they are stronger bases than ammonia and preferentially attack the substrate. However, the reaction is very useful for the preparation of tertiary amines and quaternary ammonium salts. If ammonia is the nucleophile, the three or four alkyl groups on the nitrogen of the product must be identical. If a primary, secondary, or tertiary amine is used, then different alkyl groups can be placed on the same nitrogen atom. The conversion of tertiary amines to quaternary salts is called the Menshutkin reaction It is sometimes possible to use this method for the preparation of a primary amine by the use of a large excess of ammonia or a secondary amine by the use of a large excess of primary amine. The use of ammonia in methanol with microwave irradiation has also been effective. Microwave irradiation has also been used in reactions of aniline with allyl iodides. A base other than the amine... 

Secondary, tertiary amines and quaternary ammonium salts are bitter, especially alkaloids, antibiotics and quaternary ammonium drugs... 

High molecular-weight amines are of particular importance in the extraction [35-39]. They form ion-associates with acids (e.g., HSCN, HReOa, HI), metal-complex acids [e.g., H2PtCl6, HFeCU, H2U02(S04)2]2, and heteropoly acids. These complexes are extractable into non-polar solvents (e.g., CeHa, CHCI3, CCI4) and polar solvents (e.g., MIBK, amyl alcohol). Tertiary amines, such as tribenzylamine (TBA) and tri-n-octylamine (TOA) are most commonly used. Tertiary and secondary amines are used for extraction of anions from acid solutions, whereas quaternary ammonium salts enable also extraction from neutral and alkaline solutions. Secondary and tertiary amines and quaternary ammonium salts are applied as solutions in non-polar solvents. Diphenylguanidine (formula 1.13) is also frequently used in extraction. 

Purely aromatic or purely aliphatic tertiary amines and quaternary ammonium salts do not react with nitrous acid, but mixed aromatic-aliphatic amines of the dimethylaniline type form green or yellow p-nitroso derivatives (Figure 3.5.4) when treated with nitrous acid. This reaction has also been used for the determination of nitrites. 

The first amino substituted boronic esters were tertiary amines derived from dibutyl (iodomethyl)boronate and secondary amines [58]. Mysteriously, ammonia did not yield the simple (aminomethyl)boronic ester, but ilure of a reaction does not prove anything. Subsequent rechecking with primary, secondary, and tertiary amines as reactants showed that primary amines with dibutyl (iodomethyl)boronate did not yield isolable primary (aminomethyl)boronic esters [59]. The tertiary amines and quaternary ammonium salts derived from secondary and tertiary amines were stable and easily isolable. 

A-Methylation. The direct monomethylation of ammonia or a primary amine with methyl iodide is usually not a feasible method for the preparation of primary or secondary amines since further methylation occurs. However, methylation of secondary and tertiary amines leading to the production of tertiary amines and quaternary ammonium salts, respectively, is a useful method. 

Mohamed, F. A., A. I. Mohamed, H. A. Mohamed, S. A. Hussein, Quercetin for determination of some tertiary amine and quaternary ammonium salts, Talanta, 1996,43,1931-1939. 

Alkylation (Section 22 12) Amines act as nucleophiles toward alkyl halides Pri mary amines yield secondary amines secondary amines yield tertiary amines and tertiary amines yield quaternary ammonium salts... 

The benzylation of a wide variety of aHphatic, aromatic, and heterocycHc amines has been reported. Benzyl chloride is converted into mono-, di-, and tribenzyl amines by reaction with ammonia. Benzylaniline [103-32-2] results from the reaction of benzyl chloride with aniline. Reaction with tertiary amines yields quaternary ammonium salts with trialkylpbospbines, quaternary phosphonium salts and with sulfides, sulfonium salts are formed. 

Further alkylation of tertiary amines yields quaternary ammonium salts. These compounds are numerous and are readily prepared by heating the alkyl halide and tertiary amine in the absence of a solvent or in the presence of alcohol. Methylation of tertiary amines to quaternary ammonium salts can be accomplished with methyl halides or dimethyl sulfate. ... 

Polymers with different end groups usually also have differences in thermal stability. It has been found that tertiary amines or quaternary ammonium salts initiated chloral polymers have very poor thermal stability. Triphenyl phosphine initiated polychloral samples have good thermal stability and the lithium tertiary butoxide initiated polychloral has a thermal stability close to that of the phosphine initiated polymers. 

Some amines which extract anions from aqueous solutions as ion pairs are called liquid anion exchangers [40,41]. They are marketed commercially under such trade names as Aliquat-336 and Amberlite LA-1. They are mixtures of secondary or tertiary amines, or quaternary ammonium salts, with alkyl groups having 7-12 carbon atoms. 

In an acidic medium (pH-1.7) and at a temperature not higher than 10°C, chromium(VI) reacts with H2O2 ( 0.02 M) to form blue perchromic acid which can be extracted into ethyl acetate, isoamyl alcohol, or similar oxygen-containing solvents. These methods permit the separation of Cr from V, Fe, and most other metals [7j. Perchromic acid can also be extracted with solutions of tertiary amines or quaternary ammonium salts [8,9]. 

Dichlorocarbene Dichloronorcarane can be prepared in about 75% yield from cyclohexene, chloroform, and an aqueous solution of sodium hydroxide in the presence of tri-n-butylamine or the hydrochloride as catalyst. Some other tertiary amines or quaternary ammonium salts are equally effective tetra- -butylammonium bromide, N-n-butylpiperidine, N,N-di-n-butylpiperidinium iodide. No primary or secondary amines were found to have this catalytic activity. 

Amines can be prepared by the alkylation of ammonia. In this array of reactions (Figure 27-2), the amines nucleophilically attack the alkyl halides. As shown below, the first reaction yields a primary amine. Primary amines yield secondary amines which in turn yield tertiary amines, and tertiary amines yield quaternary ammonium salts. 

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. 

Cationic alkylamine extractants were introduced in 1948 (Smith and Page 1948) for uranium production on an industrial scale. A few years later similar reagents based on phosphorous or arsenic, e.g., tetraphenylphosphonium and tetraphenylarsonium cations were introduced (Tribalat 1949). Today tertiary amines like trioctylamine extractants play a very important role in uranium production. Amines and quaternary ammonium salts are also used for production of many other metals, e.g., rare earth metals. 

III) tricarboxylate salts. Cyclic carboxylic acid anhydrides, for example, phthalic anhydride, give polyesters with PO. The reaction is catalyzed by diethyl zinc, lithium chloride, tertiary amines, and quaternary ammonium halides. 

Limitations are also imposed by the nature of the alkyl group in the alkyl halide. Broadly speaking, the alkyl halides which react with ammonia (or amines) to give amines and quaternary ammonium salts are those which are susceptible to substitution by the 3, 2 mechanism. Amines preparable by this route are consequendy those in which primary or secondary alkyl groups are attached to the nitrogen atom. Attempts at alkylation of ammonia and amines using tertiary alkyl halides are normally frustrated by the occurrence of alternative elimination reactions and such problems are also apparent with other halides in which structural features favour alternative reactions (reaction 24) An important group of tertiary halides which may be... 

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