Sulfur quaternization

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). 

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). 

On boiling the methiodide with 70% sulfuric acid an N-methyl-oxo derivative was obtained, and this in turn gave 3-amino-2-phenyl-quinoline, methylamine, and ammonia on fusion with soda lime. The bulk of the evidence therefore favors quaternization at N-2 (cf, 154), in which case the acid-hydrolysis product is 155. Quaternization at N-2 would be expected because of the steric influence of the 10-phenyl group and the influence of the 4-amino group (cf. 4-hydroxy-pyridazine ) in the pyridazine-type ring, although the partial double-bond character of that ring is probably different from that in pyridazine itself. 

The acid-catalyzed cyclization of salts (188 Scheme 101) prepared from 2-cyanopyridine by quaternization with a benzyl halide provides the only method yet developed for the synthesis of 11-aminoacridzinium salts (189). The prototype quaternary salt (188 R = H) was cyclized in sulfuric acid in an overall yield of 25% (73JOC4167). A better yield (59%) was obtained when the point of electrophilic attack was activated by a para methoxy group. 

Other solvents also are not inert to the alkylating agent. For example, DMSO and Mel react, first (reversibly) at oxygen and then at sulfur.45 This side-reaction becomes important only in quaternization studies involving poorly nucleophilic heteroaromatic substrates.41... 

Quaternization of the sulfur atom followed by reaction with mercuric cyanide produces the corresponding 2-aminomalononitrile.64171... 

In analogy to the transformations observed for other compounds, a similar process was proposed for the interconversion of thiaspirane sulfoxides and to explain the dependence of the thermolytic process on sulfoxide stereochemistry. Scheme 1 shows the probable mechanism of the transformation. Stereochemical transformations of the C30 Nuphar thiaspiranes have been observed on quarter-nization of thiobinupharidine (16) (equatorial sulfur atom). The quaternized quinolizidine system is transformed from the trans to the cis form with inversion of the relative configuration of the corresponding C-7 or C-7. ... 

In alkaloids with an axial sulfur atom (neothiobinupharidine (17) and thio-nuphlutine B (18), in addition to quaternization on nitrogen, methylation on sulfur also takes place (60, 61). The rate of sulfonium salt 56 formation as compared with quaternization must be greater since they are formed in the first step. It was observed that monomethiodides of sulfonium salts can be transformed to... 

The quantitative effects of -substituents in decreasing the rates of these reactions are not additive and also depend considerably on solvent and alkylating agent. They are low in liquid sulfur dioxide as a solvent where solvation effects are small and the high dielectric constant increases the bond breaking in the transition state. For 3- and 4-substituted pyridines a Br nsted correlation exists between the rates of quaternization and the pKa values <1978AFIG(22)71 >. 

Various l-alkylimidazo[l,2-a]pyrazine 7-oxide quaternary salts have also been synthesized from imidazoles (71JCS(C)2748). Two approaches were used. Quaternization of the oximes (462) with a-bromocarbonyl compounds gave salts (463) which cyclized in strong acid to the 7-oxides (464), and quaternization of the acetals (465) with bromoacetaldehyde oxime afforded salts (466) which were treated with concentrated sulfuric acid. 

Evidence in support of formula CXXXII came recently from the characterization by synthesis 101) of the dimethiodide CXXXVII obtained through the oxidation of tiliacorine with manganese dioxide-sulfuric acid. The sjmthesis of CXXXVII involved treatment of 2,7-bis(2-aminoethyl)-4,9-dimethoxydibenzo-p-dioxin (CXXXVIII) with formic acid to give the diformyl derivative CXXXIX and cyclization of the latter with phosphorous oxychloride followed bj quaternization. 

Another approach used for deactivating part of the amine groups of polyethylenimine was to use a partial quaternization of polyethylenimine with ethyl iodide. The membranes formed were similar in properties to those made by the partial polyethylenimine neutralization. Still another type of amine polymer was prepared by free radical polymerization of a mixture of diallylamine hydrochloride, dimethyl diallyl ammonium chloride and sulfur dioxide. This polymer in the free base form for interfacial reaction had reactive secondary amine groups and non-reactive quaternary amine groups ... 

Curiously, when liquid sulfur dioxide is used as a solvent and Mel as the quaternizing agent, one ortho methyl group retards the rate by 1% and the second by 44%. Although nonadditivity is observed, these kinetic effects are surprisingly small. 

Benzo[c]cinnoline is a weak base with a of 2.2 in water and 1.6 in 50% aqueous ethanol.Cryoscopic measurements show that it is dipro-tonated to some extent in 100% sulfuric acid. Well-defined quaternary salts result from heating benzo[c]cinnoline with alkyl halides and sul-fates. These are reported to decompose on treatment with ammonia, regenerating benzo[c]cinnoline, but apparently nucleophilic displacements of halogen by amines have been carried out on certain highly substituted examples in the synthesis of cationic dyestuffs. Quaternizations of benzo[c]cinnoline with a,a)-dibromo-propane and -butane are accompanied by hydrogen bromide elimination to give the cyclic iminium salts 40 and 41. When 40 is dehydrogenated, or merely refluxed in ethanol. 

When 1 -methylimidazole is quaternized at N-3 by 4-methoxybenzyl chloride, the salt deprotonates readily in the presence of sodium hydride in DME. 1,3-Dimethylimidazolium salts react analogously, allowing access to 2-chloro-, 2-bromo-, 2-deutero-, and various 2-substituted phosphorus- and sulfur-containing imidazoles <8877413>. 

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