Quaternization

In situ quaternization method ethyl 2-(ethoxycarbonyl)-2-formamido-3-(indol-3-yl)propanoate[7,8J... 

Prior quaternization method 4-acetyl-4-cyano-5-(indol-3-yl)pentan-2-one[9]... 

As in the pyridine series, acid catalysis facilitates this reaction because the 2-position of the ring is far more sensitive to the nucleophilic reagents when the nitrogen is quaternized (30). 

Quaternary salts (33) obtained from aminothiazole derivatives liberate 2-imino-4-thiazolines in basic medium (Scheme 24). This reaction is general and independent of the nature of R in 33 (160-167). The same result was found when 2-propynylbromide (168) or 3-chloropropionic acid (169) were the quaternizing reagents. This method is particularly... 

Thiazolium salts can be obtained either directly by slight modifications of ring-closure methods, already described for the parent bases, or by classical quaternization of the bases, the detailed mechanism of which have been reported in Chapter III the quaternization is best represented by a classical SNj mechanism, the solvent playing an important part (14) unless the reaction is run without any solvent. 

The mobility of the proton in position 2 of a quaternized molecule and the kinetics of exchange with deuterium has been studied extensively (18-20) it is increased in a basic medium (21-23). The rate of exchange is close to that obtained with the base itself, and the protonated form is supposed to be the active intermediate (236, 664). The remarkable lability of 2-H has been ascribed to a number of factors, including a possible stabilizing resonance effect with contributions of both carbene and ylid structure. This latter may result from the interaction of a d orbital at the sulfur atom with the cr orbital out of the ring at C-2 (21). 

These dyes possess two independent chromophoric chains of even methine (neutro) and uneven methine (cyanine) fixed on a central ketometbylene nucleus. The methylene reactive group is first used for the neutrocyanine synthesis in position 5. the, quaternization of which can ensure a subsequent polymethine synthesis in position 2 of a cationic dye by ordinary means (Scheme 58). As indicated, this quaternized neutrocyanine (37) may as well give another neutrocyanine. 

As in the case of pyridine (185), the quaternization of thiazole induces a bathochromic shift of the ultraviolet absorption spectrum in ethanol the long wavelength maximum at 232.3 nm (3900) for thiazole moves to 240 nm (4200) for 3-methylthiazolium tosylate (186) (Table 1-19). 

Potts et al. (333) condensed dipolarophiles (DMA, dibenzoylacetylene, ethyl propiolate) with ylides (81) obtained by quaternization of 4-methyl-thiazole with an a-bromoketone or ester and subsequent deprotonation. In fact the 1 1 molar adduct obtained (82) rearranged to a pyr-rolothiazine (83). One example of this reaction is described Scheme 49. 

Although isothiazole (pK = 1.90) is less basic than thiazole, its rale of quaternization by dinitrophenyl acetate in water at 52°C is approximately 2.5 times higher (447). This deviation from the Bronsted relationship (A log k - 0.ApK, with positive) is interpreted as a consequence of the or effect of the adjacent sulfur lone pair in isothiazole that is responsible for its higher nucleophilicity (448, 449). 

If the rate constants for quaternization of 2-alkylthiazoles depended on electronic factors, they would all be greater than that of thiazole, which has the low est pK. and all of the same order. The decrease in rate constants that is observed is attributed wholly to steric effects. In Table III-50 we report the main parameters for the reaction of 2-alkylthiazoles with methyl iodide. 

The role of the quaternization of the azasubstituent in the nucleophilic substitution at 2-halogenothiazoles is in fact emphasized by the reactivity of 2-halogenothiazoles with undissociated thiophenol (35), which proceeds faster than the corresponding reaction of 2-halogenothiazoles with thiophenolate anion, through the pathways shown in Scheme 6. Moreover, the 4-halogenothiazoles do not react with undissociated thiophenols, while the 5-halogenothiazoles react well (48). 

Strauss and Williamst have studied coil dimensions of derivatives of poly(4-vinylpyridine) by light-scattering and viscosity measurements. The derivatives studied were poly(pyridinium) ions quaternized y% with n-dodecyl groups and (1 - y)% with ethyl groups. Experimental coil dimensions extrapolated to 0 conditions and expressed relative to the length of a freely rotating repeat unit are presented here for the molecules in two different environments ... 

Polyamines can also be made by reaction of ethylene dichloride with amines (18). Products of this type are sometimes formed as by-products in the manufacture of amines. A third type of polyamine is polyethyleneimine [9002-98-6] which can be made by several routes the most frequently used method is the polymeriza tion of azitidine [151 -56 ] (18,26). The process can be adjusted to vary the amount of branching (see Imines, cyclic). Polyamines are considerably lower in molecular weight compared to acrylamide polymers, and therefore their solution viscosities are much lower. They are sold commercially as viscous solutions containing 1—20% polymer, and also any by-product salts from the polymerization reaction. The charge on polyamines depends on the pH of the medium. They can be quaternized to make their charge independent of pH (18). 

QuaterniZation. Quaternary ammonium compounds are formed by alkylation of alkyl, alkyl dimethyl, dialkyl, and dialkylmethyl fatty amines with methyl chloride, dimethyl sulfate, or benzyl chloride (1,3,7,12,29). 

Fats, Oils, or Fatty Acids. The primary products produced direcdy from fats, oils, or fatty acids without a nitrile iatermediate are the quatemized amidoamines, imidazolines, and ethoxylated derivatives (Fig. 3). Reaction of fatty acids or tallow with various polyamines produces the iatermediate dialkylarnidoarnine. By controlling reaction conditions, dehydration can be continued until the imidazoline is produced. Quaternaries are produced from both amidoamines and imidazolines by reaction with methyl chloride or dimethyl sulfate. The amidoamines can also react with ethylene oxide (qv) to produce ethoxylated amidoamines which are then quaternized. 

Quaternized Esteramines. Esterquatemary ammonium compounds or esterquats can be formulated into products that have good shelf stabihty (209). Many examples of this type of molecule have been developed (see Fig. 1). 

Quaternized esteramines are usually derived from fat or fatty acid that reacts with an alcoholamine to give an intermediate esteramine. The esteramines are then quaternized. A typical reaction scheme for the preparation of a diester quaternary is shown in equation 9 (210), where R is a fatty alkyl group. Reaction occurs at 75—115°C in the presence of sodium methoxide catalyst. Free fatty acids (230) and glycerides (231) can be used in place of the fatty acid methylester. 

Quaternary ammonium alkyl ethers are prepared similarly an alkaline starch is reacted with a quaternary ammonium salt containing a 3-chloto-2-hydtoxyptopyl or 2,3-epoxyptopyl radical. Alternatively, such derivatives can be prepared by simple quaternization of tertiary aminoalkyl ethers by reaction with methyl iodide. Sulfonium (107) and phosphonium (108) starch salts have also been prepared and investigated. Further work has explained the synthesis of diethyl aminoethyl starch (109) as well as the production of cationic starches from the reaction of alkaline starch with... 

The first synthesis of amphiphilic porphyrin molecules involved replacement of the phenyl rings in TPP with pyridine rings, quaternized with C2QH 2Br to produce tetra(3-eicosylpyridinium)porphyrin bromide (3) (36). The pyridinium nitrogen is highly hydrophilic the long C2Q hydrocarbon serves as the hydrophobic part. Tetra[4-oxy(2-docosanoic acid)]phenyl-porphyrin (4) has also been used for films (37). 

Tetraalkyl and tetraaryl compounds, R SbX, are well-known and are often referred to as stibonium salts. There is evidence, however, that most of the tetraaryl compounds contain pentacovalent antimony. The perchlorate [(C3H3)4Sb](ClO, however, is ionic (186). The tetraalkyl haUdes are readily prepared by quaternization of the corresponding tertiary stibiaes ... 

Aston MS Refinex Onyx quaternized (cationic) fatty amine condensate... 

The method described in reference 6 differs only in that quaternization is an additional step. 

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). 

Other polyamine derivatives are used to break the oil/water emulsions produced at times by petroleum wells. Materials such as polyether polyols prepared by reaction of EDA with propylene and ethylene oxides (309) the products derived from various ethyleneamines reacting with isocyanate-capped polyols and quaternized with dimethyl sulfate (310) and mixtures of PEHA with oxyalkylated alkylphenol—formaldehyde resins (311) have been used. 

A related effect is observed on quaternization, but in this case the operation of a (3-substituent effect results in the overall change at the a carbon atom normally being small (Table 5). A further important general trend in the azines arises on A-oxidation, which... 

A nitrogen atom at X results in a variable downfield shift of the a carbons, depending in its extent on what else is attached to the nitrogen. In piperidine (45 X = NH) the a carbon signal is shifted by about 20 p.p.m., to ca. S 47.7, while in A-methylpiperidine (45 X = Me) it appears at S 56.7. Quaternization at nitrogen produces further effects similar to replacement of NH by A-alkyl, but simple protonation has only a small effect. A-Acylpiperidines show two distinct a carbon atoms, because of restricted rotation about the amide bond. The chemical shift separation is about 6 p.p.m., and the mean shift is close to that of the unsubstituted amine (45 X=NH). The nitroso compound (45 X = N—NO) is similar, but the shift separation of the two a carbons is somewhat greater (ca. 12 p.p.m.). The (3 and y carbon atoms of piperidines. A- acylpiperidines and piperidinium salts are all upfield of the cyclohexane resonance, by 0-7 p.p.m. 

The couplings of other magnetic nuclei to nitrogen have been studied the reader should refer to Axenrod s chapter in the monograph of Witanowski and Webb for details bond coupling in quaternized heterocycles... 

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