Preparation of Quaternary Ammonium Salts

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). 

The formation of charged molecules within hydrophobic supports does not proceed as smoothly as in polar solvents. For instance, high reaction temperatures are required to quaternize polystyrene-bound phosphines [335,336], and the N-benzylation of pyri-dines with Merrifield resin also proceeds sluggishly [37]. Quaternization of tertiary 

---

The ring-chiorinated benzyl chlorides are used ia the preparation of quaternary ammonium salts and as iatermediates for pharmaceuticals and pesticides. p-C. orohen zyl chloride is an iatermediate ia the manufacture of the rice herbicide, Saturn ((S-4-chlorobenzyl)-N,N-diethylthiolcarbamate [28249-77-6] (75). The o- and -chlorobenzal chlorides (l-chloro-2-and 4-dich1 oromethylhenzenes) are starting materials for the manufacture of o- and p- chlo rob enz aldehyde s. 

This reaction is generally used for the preparation of quaternary ammonium salt. 

The amino functional group is not commonly encountered in steroid synthesis except perhaps in steroidal alkaloids. However, certain elimination reactions have been shown to have theoretical and limited preparative importance, largely due to the efforts of McKenna and co-workers. The Hofmann rule for 2 elimination predicts that alkaline elimination of quaternary ammonium salts will occur towards the carbon carrying the most hydrogen atoms cf. the converse Saytzeff orientation, above). In cyclohexyl systems, the requirement for diaxial elimination appears to be important, as in other 2 eliminations, and the Hofmann rule frequently is not obeyed [e.g., (116) (117)]. 

When potassium fluoride is combined with a variety of quaternary ammonium salts its reaction rate is accelerated and the overall yields of a vanety of halogen displacements are improved [57, p 112ff. Variables like catalyst type and moisture content of the alkali metal fluoride need to be optimized. In addition, the maximum yield is a function of two parallel reactions direct fluorination and catalyst decomposition due to its low thermal stability in the presence of fluoride ion [5,8, 59, 60] One example is trimethylsilyl fluoride, which can be prepared from the chloride by using either 18-crown-6 (Procedure 3, p 192) or Aliquot 336 in wet chlorobenzene, as illustrated in equation 35 [61],... 

Amine oxides 2, which can be prepared by oxidation of amines 1, react upon heating to yield an olefin 3 and a hydroxylamine 4. This reaction is called the Cope elimination reaction,and as a synthetic method is a valuable alternative to the Hofmann degradation reaction of quaternary ammonium salts. 

Typical preparation of quaternary ammonium permanganate salts... 

A portion of the wet sol-intercalated clay was mixed with a surfactant of quaternary ammonium salts [CH3(CH2)n-i N(CH3)3Br] by stirring for 2 hours. 15.75 mmol of surfactant was added to each gram of the starting bentonite clay. The resultant mixture of clay and surfactant was transferred into an autoclave and kept in an oven at 100°C for 3 days. The wet cake was washed with water to Cl ions free and the solid was recovered by filtration. The solid was dried in room temperature and calcined at 773 K. for 4 h. The calcined products were labeled as sol-PILB-Cn, where n denotes the number of carbon atoms in the alkyl chain of the surfactants used. Four samples were prepared sol-PILB-C12, -C14, -C16 and -C18. 

The pore volume and surface area of sol-PILB-Cn samples are closer to those of the corresponding MCM41 solid prepared with silica fume and the same surfactant used in the preparation of sol-PILB-Cn, rather than to that of sol PILB. For example, the total pore volume and BET specific surface area of sol-PILB-C16 are 0.84 cm3/g and 756 m2/g, respectively, much larger than those for sol-PILB, 0.24 cm3/g and 404 m2/g, but comparable to those for MCM41-C16, 0.94 cm3/g and 790 m2/g. These results suggest that treatment with surfactants of quaternary ammonium salts alters the structure of the sol pillared clay radically. 

Emulsifying agents have been prepared from quaternary ammonium salts with silicon in the cation. There is a large number of alkyd-silicone resins. 

Being internally neutralized, the amphoterics have minimal impact on the biocidal activity of quaternary ammonium salts. For this reason, like the nonionics, they often find use in antimicrobial preparations that are based on cationic surfactants. 

We have already encountered alkylation of amines as a side reaction in the preparation of primary amines by the ammonolysis of halides (Sec. 22.10), and as a method of synthesis of secondary and tertiary amines (Sec. 22.13). Let us look at one further aspect of this reaction, the formation of quaternary ammonium salts. 

Most interest in biological activity has been centered on 4,5,6,7-tetra-hydrothieno 2,3-c, - or - 3,2-c pyridines. A considerable number of derivatives of these systems have been prepared by the sodium borohy-dride reduction of quaternary ammonium salts,90,91 or by reaction of the 4,5,6,7-tetrahydro base with a suitable halide,9,I°4 tosyl derivative,105 epoxide,106 or activated alkene.107 An alternative, and very convenient, synthesis of 2-amino-3,6-substituted 4,5,6,7-tetrahydrothieno[2,3-c[-pyridincs (89), used mostly by Nakanishi and his co-workers, involves reaction of an N-substituted 4-piperidone, a compound of the type 88 and sulfur, in the presence of morpholine. The group X can be CN,... 

Eliminations. A new preparation of a-substituted acrylonitriles involves a twofold elimination of quaternary ammonium salts. ... 

OTHER COMMENTS used in the preparation of quaternary ammonium compounds ingredient of photographic development accelerator, for drying of printing inks, and in carpet cleaners used as a corrosion inhibitor and as an accelerator for rubber used as a catalytic solvent in chemical synthesis also used in the desalination of seawater use in non-nutritive sweeteners, ketenes, and salts. 

Another method to solubilize organometallic compounds in water is the incorporation of quaternary ammonium salts (Figure 10). A characteristic member of this group is the AMPHOS ([Ph2P-(CH2)2-NMe3] CU) 18, which could be prepared from Ph2P-(CH2)2-NMe provided the phosphorus atom is protected by oxidation or coordination to a transition-metal center before forming the ammonium salt. ... 

Multilayer composite surfaces prepared by an electrostatic self-assembly of quaternary ammonium salt or tetramethyl ammonium chloride and polyacrylic acid onto poly (acrylonitrile-co-acrylic acid) membrane... 

Highly ethoxylated amines and diamines have been recommended for demulsification of crude oil. Combinations of quaternary ammonium salts and amines oxides are useful for foaming and silt suspension. Coco alkyltrimethylammonium chloride and bis(2-hydroxy-ethyljcoco alkylamine oxide comprise the preferred combinations. Quaternary ammonium salts, including coco alkyltrimethylammonium chloride, are useful for preparing foamed oil-in-water emulsions, which can dissolve paraffins and asphaltenes without formation damage. The pyrolized amine salts of humic acid have been used in filtrate control additives. 

The biggest difference involved in describing an organoclay is the type of quaternary ammonium salt(s) used to prepare it. Although most commercial products are made from three types of quaternaries, namely dimethyldi(hydrogenated tallow)ammonium chloride, dimethylbenzyl(hydrogenated allow)ammonium chloride, and methylbenzyldi(hydrogenated tallow)ammo-nium chloride, many other quaternaries have been used and described in the patent literature. 

Lithium n-propylmercaptide in hexamethylphosphoramide provides a mild system for the rapid dealkylation of quaternary ammonium salts, with high propensity for methyl group removaL. Substituted amidines have been prepared under very mild conditions from nitriles, halides, and amines with the help of a Lewis acid such as ferric chloride . a,a-Dichloro-/ -ketoesters undergo a rapid fragmentation with nucleophiles, even with relatively weak ones such as diethylamine, and can thus serve as acylating agents... 

---