Tertiary amines quaternization

QuaterniZation. Choline chloride [67-48-1] was prepared ia nearly quantitative yield by the reaction of trimethylamine [121-44-8] with ethylene chlorohydrin at 90—105°C and 981—1471 kPa (10—15 kg/cm ) pressure (44). Precursors to quaternary ammonium amphoteric surfactants have been made by reaction of ethylene chlorohydrin with tertiary amines containing a long chain fatty acid group (45). 

The nitrogen atom in quinolizidine derivatives behaves as a tertiary amine and hence it can undergo quaternization by reaction with alkyl halides. For instance, berberine derivative 101 was transformed into 102 by treatment with 3-iodopropanol followed by anion exchange. Compound 102 was then transformed into intermediate 103, which was employed as a precursor for the the preparation of bis-ammonium salt 104 (Scheme 10). This compound showed ultrashort curare-like activity in rhesus monkeys <2001JOC3495>. 

The direct quaternization of chloromethylated polystyrenes by tertiary amines or phosphines represents the easiest way to obtain polymer-supported quaternary onium salt (12,13). A lipophilic character of quaternary cation and a topology allowing sufficient cation-anion separation also play an important role (35,36). A linear spacer chain (of about 10 carbon atoms) between the catalytic site and the polymer backbone substantially increases the reaction rates. The loading of quaternary onium groups also affects catalytic efficiency, the influence being different for directly bonded and spaced groups, e.g. 10 and 11, respectively (37). 

Molecular weights of the products as measured with vapor pressure osmometry were in good agreement with the calculated ones. Interestingly, resins based on hexahydrophthalic anhydride and diisopropanolamine with tertiary amines as functional groups are soluble in water without quaternization of the... 

Heterocyclic amines have also been used as phase transfer catalysts. However, because these amines quaternize easily, the question is whether the operative catalyst is the tertiary amine or the quaternary ammonium salt formed in situ Furukawa et al.286 have shown that a methyl 2-pyridyl sulfoxide may be used as a phase transfer catalyst and promote substitution reactions between lithium chloride or sodium cyanide and benzyl bromide. According to the authors, the catalyst behaves as a cation complexer and not as a quaternary ammonium salt formed in situ by a Menschutkin reaction. 

Base-induced (3-elimination of quaternized amines can be mediated by amines (including ammonia [468]) or by basic ion-exchange resins [469,470]. Because non-qua-ternized amines, which are potential by-products in this synthetic sequence (Figure 3.28), do not undergo [3-climination as readily as the quaternized ammonium salts, pure tertiary amines are generally obtained by this technique. 

The only drawback of strategies for the synthesis of tertiary amines that are based on the quaternization of polystyrene-bound /V-nucleophiles is that quaternizations on polystyrene only proceed sluggishly and generally require the use of highly reactive alkylating agents (methyl, allyl, or benzyl halides or sulfonates see Section 10.2). 

The quaternization of tertiary amines on cross-linked polystyrene has been investigated in detail. The most commonly used substrates in these studies have been N,N-dialkyl- 3-alanine derivatives because, after their quaternization, pure tertiary amines can be released from the support by treatment with a base (see Section 3.7). 

Table 10.16. Quaternization of support-bound tertiary amines.

Tertiary Amine-Containing Copolymers. Copolymers based on DMAEMA (dimethylaminoethyl methacrylate) in either free amine form or quaternized with diethyl sulfate or methyl chlonde have achieved commercial significance as fixatives in hair-styling formulations, especially in the well-publicized mousses" or as hair-conditioning shampoo additives. 

Here, we envisage building the benzimidazole scaffold directly onto the linker and, by analogy with a regular tertiary amine synthesis on the REM linker, we can quaternize the resin-bound benzimidazole compounds by reaction with reactive bromides. The quaternary salt can then be liberated by a Hofmann elimination reaction upon treatment with base. 

Reaction of 9-chloroacridine with aryl sulfonyl hydrazides results in aminodechlo-rination to give the corresponding A-acridinylbenzenesulfonyl hydrazides kinetic studies in methanol and DMSO have been reported.44 Reaction of electron-deficient heteroaryl chlorides with tertiary amines may proceed by quaternization and dealkylation, as shown in Scheme 3. These reactions occur under mild conditions, e.g. acetonitrile solvent at room temperature, and in THF may be accelerated by the addition of lithium chloride.45... 

Simple tertiary amines are difficult to deprotonate selectively [195, 196, 200], To increase the acidity of the a-C,H-groups the amine can be quaternized [207], treated with a Lewis acid [208-211], oxidized to an amine N-oxide[161], or, for secondary amines, derivatized with a functional group capable of forming a chelate with the metal (Scheme 5.22). 

The wide availability of relatively inexpensive dimethylaminopropylamine (DMAPA) allows surfactant producers to convert economic triglycerides, fatty acids and methyl esters into amido -functional tertiary amines that may then be quaternized with sodium chloroacetate to produce alkylamidopropyl betaines (see Figure 6.15). The most economically significant of these is cocamidopropyl betaine which can be produced from a variety of feedstocks and lauramidopropyl betaine which is generally produced from lauric acid. These are widely used secondary surfactants in consumer products such as shampoos, bath products, washing up liquids and other cleaners. 

It is well known that amines can be neutralized with acids to generate salts. This neutralization process is useful in preparing organic salts with very low melting points. In 1914 Walden reported [3] neutralized ethylamine with nitric acid to prepare a salt that had a melting point of 12°C. This appears to have been the first ionic liquid prepared by a neutralization method [4]. As seen in equation (19.1), there is a slight difference between onium cations prepared by quaternization (a) and neutralization (b) when tertiary amines are used as a starting material ... 

Polycarbobetaines may be synthesized via a number of reaction pathways by functionahzation of suitable monomers or polymers, most commonly by reaction of a tertiary amine with a strained lactone, an a, -unsaturated acid, a haloalkylcarboxylate, or a haloalkylcarboxyhc ester followed by hydrolysis of the ester. Alternatively, the quaternization of halogen-containing... 

Quaternization of poly(4-VP) with alkyl halides and reaction of poly(VBC) with various tertiary amines result in cationic polyelectrolytes with a variety of charge density and of the hydrophilic-hydrophobic ratio of... 

Uses. Tetramethylene sulfone has high solvent power for aromatics and has been used extensively by Olah and co-workers for Friedel-Crafts type nitrations and for studies of the mechanism of nitronium tetrafluoroborate nitration of alkyl-benzenes and halobenzenes in homogeneous solution. It is a superior solvent for quaternization of tertiary amines with alkyl halides, since it has a high dielectric constant and does not enter into side reactions observed with nitrobenzene and dimethylformamide. For example in the synthesis of the acridizinium salt (3), Bradsher and Parham effected quaternization of (1) with benzyl bromide in tetramethylene sulfone at room temperature in excellent yield. Several other salts analagous to (2) were obtained in good yield and in crystalline form with use of tetramethylene sulfone, whereas with other solvents the products were colored... 

The classical Hofmann elimination reaction (which dates back to 1851) has been adapted to the solid phase in combination with the Michael addition. The REM resin, called this way because the resin tinker is REgenerated after product cleavage and functionalized by means of a Michael addition, has been developed to prepare arrays of tertiary amines. The procedure involves acylation of hydroxy-methylpolystyrene with acrylic chloride to furnish the acrylate on resin. Then, a secondary amine, whose substituents offer two potential sites of diversity, is bound by Michael addition. Quaternization of the amine with an alkyl halide (or reductive animation) introduces another site of diversity and activates the tinker to release the amine by a Hofmann elimination with DIEA (Figure 15.14) [127-129]. Additionally, the use of a second basic resin has been described as a source reagent to promote the elimination [130, 131]. 

TRAM linker by Belshaw et al. [45] and the REM resin by Morphy et al. [46] should be mentioned here, as they are built on a quaternization strategy of amines as activation step and subsequent (3-elimination by basic treatment as well. While the REM resin releases tertiary amines from the solid support, the use of the TRAM linker yields Michael acceptors. 

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