Quaternization, by alkyl halides

Monocyclic Phosphoranide Anion. The intramolecular oxidative addition of hydroxyalkyl phosphites, which gives P-H phosphoranes, is well known (10). Some P-H phosphoranes are so stable that the open-chain P(III) tautomers cannot be detected spectroscopically or even by attempted H2O2 oxidation (8). Thus, it is surprising to find no evidence for an equilibrium between phosphine alcohol 1 and its closed-ring tautomer phosphorane 2. Phosphine 1 is quaternized by alkyl halides giving phosphonium halides such as 3. These in turn are converted to alkoxyphosphor-anes, such as 4 by NaH (Scheme I). 

Amino-1,2,4-triazoles (50) or their derivatives are usually starting material for the synthesis. They are readily available and already contain the exocyclic N-N bond required for heteroaromatic A-imines. 4-Amino-1,2,4-triazoles can be quaternized by alkyl halides or tosylates at the N-l atom to give the salt 52.79-82 (Scheme 5) The orientation of quatemization is proved by the reactions in Scheme 6 for the example of the quaternary acylamino salts 52. Quaternary salts of the type 52 can also be prepared by reaction of 1,3,4-oxadiazolium salts (51)83 with aryl hydrazines84 and from aryl hydrazine hydrohalides and orthoesters.86 With alkali, the 1-alkyl-s-triazole-4-imines8(7-82 86 can be obtained in the normal manner from these salts (Scheme 5). The free A-imines are all stable except the A-unsubstituted compound itself.87 Recently, other structures were tentatively reported 88 for the deprotonation products of analogous quaternary salts (52) with hydrazine. 

Tertiary phosphines are rapidly quaternized by alkyl halides. During the reaction with the ambident triethoxycarbenium fluoroborate, phosphines seek the softer ethyl group (3). 

Quaternary salts, isolation of, 10 Quaternization, by alkyl halides, 2-7 by aryl halides, 7-9 on carbon, 53 definition of, 2 by dimethyl sulfate, 9 electronic effects in, 11 in JV-heterocycles, 16, 38 by heterocyclyl halides, 7—9 isotope effect on, 55 mechanism of, 53-56 by methyl euyl-sulfonates, 9, 10 on oxygen, 52 rates of, 55 reagents for, 2-10 by self-condensation, 8 solvent effect on, 10, 55 solvents for, 10 steric effects on, 12, 13 substituents, influence on, 11, 19, 23 on sulfur, 51 Quinaldine, 4-amino-, 4 Quinazolines, 2-alkyl-, salt formation of, 6... 

Quaternization of TP, e.g., by alkyl halide and tosylate or phenacyl halide, always attacks N-3 [79UP1 85JCS(P1)2333] as demonstrated by degradation (68JHC691). 

Thiazoles readily undergo AT-alkylation by alkyl halides or tosylates (Menshutkin reaction). The sensitivity of this SN2 quaternization reaction to the molecular environment of the nitrogen atom has been used to evaluate, in a quantitative way, steric and electronic effects of ring substituents. The electronic effect of alkyl substituents (unperturbed by any steric effect) may be evaluated from the rate constants for the reaction of 5-alkylthiazoles with methyl iodide (in nitrobenzene at 30 °C) Table 19 shows that introducing a methyl group at the 5-position corresponds to an acceleration of the rate by a factor of 2 but that each addition of a methyl ramification to the 5-alkyl group enhances the rate only by a factor of 1.1. The data in Table 19 fit well with a Hammett-Taft equation (3) ... 

Like triorganoantimony(V) halides, derivatives of this class had also been prepared in the middle of nineteenth century169-171). The procedure adopted, which is still the principal method for preparing the tetraalkyl antimony halides involves the quaternization of trialkylantimony with an alkyl halide13,172). Since the triarylantimony as well as diaryl-alkylantimony can not be quatemized by alkyl halides, other methods13,21,23,98,173 179 e.g., the reaction of triphenylstibine, chlorobenzene and anhydrous aluminium chloride179), have been utilized to prepare these derivatives. 

On quaternization with alkyl halides, 2-quinolyl-4-quinolyl-methanes yield isocyanines and di-(4-quinolyl)methanes the corresponding cyanines. Quinolylamines give azacyanines in an analogous way. Since cyanine dyestuffs are readily prepared by condensation of the A-alkyl quaternary compounds39,40 of quinolylmethanes and -amines, by reactions analogous to those described in Section II, A, 1, the method of preparation involving alkylation of the parent compounds is of little practical use. 

In early work, certain seven-membered and larger cyclic arsines were characterized by preparation and isolation of their arsonium salts by quaternization with alkyl halides. Reaction of more elaborate seven-membered cyclic arsines with activated alkyl bromide is shown in Equation (1). The C2-symmetric chiral tertiary arsine 61 reacts with methyl bromoacetate in a pressure tube under microwave irradiation to give the arsonium salt 62 in 71%. The latter was employed in the enantioselective olefination of 4-substituted cyclohexanes via the corresponding stabilized ylide <2002TA2187>. 

Quaternary salts, ultraviolet absorption, 50 Quaternization, of alkylthiazoles, by alkyl halide or methyl tosylate, 386 of 5-alkylthiazoles, kinetic data, 391 of dialkyl thiazoles, kinetic data, 389 kinetic data, 388... 

Methylarsines and methylstibines are subject to a number of reactions such as oxidation, quaternization and complex formation, which could facilitate or inhibit their dispersal in the environment . It has been reported that environmentally important concentrations of halocarbons (Mel, MeBr and MeCl) are produced naturally and accumulate in the oceans and the atmosphere. Parris and Brinckman reported quantitative measurements of the rate of quaternization of trimethylstibine and trimethylarsine by alkyl halides in polar solvents. 

In the following text we focus on cylindrical brushes prepared by polymerization of macromonomers, in particular on two systems. First, cylindrical brushes consisting of poly-2-vinylpyridine side chains and a poly-methacrylic main chain are discussed these were converted into cationic polyelectrolyte brushes by quaternization of the pyridine units by alkyl halides. The second system comprises sulfonated anionic cylindrical brushes, i.e. polymacromonomers with polystyrene side and main chains and polymacromonomers with polymethacrylic main and polymethacrylic acid side chains. 

The quaternization of (benzo)pyridazines by alkyl halides (these systems are not readily susceptible to arylation) was reviewed in CHEC-I <84CHEC-l(3B)l>. Monoquaternization of pyridazines occurs more readily than other diazines but less readily than pyridine, reflecting the intermediate basicity/nucleophilicity of pyridazine. Diquaternization of pyridazine can only be achieved with oxonium salts, particularly Me30 BF4 . As with protonation and A-oxidation, mixtures of products are often obtained on quaternization of unsymmetrical pyridazines and have been the subject of theoretical studies. A number of 2-(ribofuranosyl)-3(2//)-pyridazinones have been prepared by stannic chloride catalyzed alkylation of 3-(trimethylsilyloxy)pyridazines with protected 1-0-ace-tylribofuranose <83JHC369>. The quaternization behavior of phthalazines is similar to that of pyridazines, but with cinnolines alkylation usually occurs at N-2, unless there is a particularly bulky substituent at C-3. 

There is rarely any difficulty in quaternizing tertiary amines by alkyl halides unless the amine is insufficiently basic or sterically hindered. Equimolar amounts of the tertiary amine and halide, best in methanol or acetone, usually afford very good to quantitative yields often in the cold and otherwise under reflux. The products are isolated by concentration of the solution and treatment with ether. 

The alkylation of amines was a highly popular method of derivatization in peptide chemistry before the practice of contemporary mass spectrometric techniques for the analysis of non-volatile compounds. Direct alkylation of amines by alkyl halides (Hoffman reaction) can finally lead to non-volatile ammonium salts and, hence, other soft reagents should be used. For example, exhaustive methylation without quaternization can be provided by the mixtures CH20/NaBH4/(H ) or CH2O/ formic acid. 

ILs can also be covalently immobilized on inorganic materials of silica, mesoporous silicates, aluminosilicate, and alumina. For that three ways are known (Scheme 10). The first method is the co-condensation of a trialkoxysdylalkyl onium salt and triethoxysilane (Scheme 10-A) [37-39]. The second one is the immobilization by the reaction between surface hydroxyl groups of the solid and the alkoxysilyl group (Scheme 10-B) [40,41]. For the last one (Scheme 10-C), the inorganic materials modified with alkyl halide (usually propylchloride) are used [42-46] on them, corresponding amine, phosphine, or pyridine can be immobilized and quaternized. For the preparation of imidazolium-based immobilized IL, imidazole is fixed on the modified support in the presence of alkali compounds, followed by quaternization with alkyl halides. 

Phthalazine forms monoquaternary salts with alkyl halides. 1-Substituted phthalazines are quaternized predominantly at position 3, and the site of quaternization of 1,4-disub-stituted phthalazines is determined by the steric hindrance of both substituents. 

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>. 

There has been much interest in diquaternary salts of 4,4 -bipyridine, the electrochemistry of which has recently been reviewed. l.l -Dialkyl diquaternary salts of 4,4 -bipyridines are prepared by treating 4,4 -bipyri-dines with excess of an alkyl halide or a dialkyl sulfate or other alkylating agent. This method has been used extensively and provides diquaternary salts of type 92 where both alkyl quaternizing groups are the same (i.e., 92 R = 211,467,689,962,967,968 Qf particular interest is the diquater-... 

Pyridinecarboxylic acids exist largely in the zwitterion form in water (57JA2050). They can be converted into esters with alcohols and mineral acid catalysis, and by use of diazoalkanes. Use of alkyl halides in alkali gives N-alkylbetaines. Esters can also be formed from acid chlorides but the latter are liable to self-quaternization. 

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