2-Methyl-4- , quatemization

A methyl quatemized erucyl amine [660] is useful for aqueous viscoelastic surfactant-based fracturing fluids in high-temperature and high-permeability formations. 

Other examples of 5-HT3 agonists besides HT are 2-methyl-HT, bufotenine, and its methyl quatemized derivative. More antagonists of clinical interest are under investigation. 

Pyridin-4-one, 1 -hydroxy-2,6-dimethyl-hydrogen-deuterium exchange reactions, 2, 196 Pyridin-4-one, 1-methyl-hydrogen-deuterium exchange, 2, 287 P a, 2, 150 Pyridin-2-one imine tautomerism, 2, 158 Pyridin-2-one imine, 1-methyl-quatemization, 4, 503 Pyridin-4-one imine tautomerism, 2, 158 Pyridinone methides, 2, 331 tautomerism, 2, 158 Pyridinones acylation, 2, 352 alkylation, 2, 349 aromaticity, 2, 148 association... 

They started synthesis by taking 2-(2,4,6-tribromo-3-methoxyphenyl)acetaldehyde 83 and (iS)-A-methylpyrrolidine-2-carboxamide 84 and achieved in two steps. Condensation of aldehyde 83 and amide 84 in anhydrous methanol yielded cyclize products 85 and 86. Stereoselective methyl quatemization of compoimd 86 yielded wilsoniamine A (80). 

While condensation of aldehyde 83 and amide 84 under TFA/toluene /reflux condition yielded only cyclize product 85, which on methyl quatemization with Me30Bp4 yielded wilsoniamine B (81) (Scheme 7) [45],... 

Mills and Smith (504) were the first, in 1922, to develop a systematic study of the reactivity of methyl groups fixed on nitrogen-containing heterocycles. While in alkylpyridines the 2- (or 6) and 4-positions are activated, only the 2-position in thiazole corresponds to an enhanced reactivity of the methyl groups in condensation with aldehydes 4- and 5-methylthiazoles bear inert methyl groups. Quatemization of the thiazole nitrogen enhances still further the reactivity of the methyl in the 2-position (cf. Chapter IX), but it does not increase the reactivity of a methyl group in the 4-position (504). The authors invoke the possibility for 2- (and 6) methylpyridine and 2-methylthiazole to pass, to some extent, into the reactive enamine form (245), while 4-methylthiazole could adopt such a structure only with the participation of an unusual formula such as 247 (Scheme 112). 

The quatemization of the nitrogen atom of the thiazole ring (the Menschutkin s reaction) by alkyl halide or methyl tosylate can be used to measure the reactivity of this atom and thus to evaluate steric and electronic effects of ring substituents. 

The first kinetic results in the area were obtained by studying the quatemization of 4-alkyl-, 5-alkyT, and 2-alkylthiazoles with methyl iodide (253-255). A deeper and more exhaustive study of this reaction has been carried out recently with more elaborate substrates (152). 

The quatemization of 16 2,4-dialkylthiazoles with methyl tosylate in nitrobenzene at 25 C has been studied (256) in order to examine the simultaneous influence of two substituents grouped around a reaction center (257). 

Fig. ni-3. Log k/ko for quatemization of allcylthiazoles versus Taft s parameters ( ) 2-alkylthiazoles, (O) 2-methyl-4-aIkylthiazoles, (X) 2,5-dimelhyl-4-alkyltfaia2oles. 

The quatemization of 5-alkylthiazoles with methyl iodide in nitrobenzene has been studied (254) results are summarized in Table III-54. 

Some studies on the quatemization of arylthiazoles have been published, among them the quatemization of 2-methyI-4-phenyl thiazole in various solvents (263). The order of reactivity is the following 2-methyl-4-phenyl > 2-methyI-4-(3-nitrophenyl) > 2-methyl-4-(2-chlorophenyl) > 2-methyl-4-(4-nitrophenyl). Introduction of a phenyl group in the... 

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. 

Tertiary Amine-Containing Copolymers. Copolymers based on DMAEMA (dimethylarninoethyl methacrylate) in either free amine form or quatemized with diethyl sulfate or methyl chloride have achieved commercial significance as fixatives in hair-styling formulations, especially in the weU-pubhcized "mousses" or as hair-conditioning shampoo additives. This success has occurred because the cationic charge affords substantive resins that strongly adhere to the hair (141). 

The most successful of these products contain high ratios of VP to DMAEMA and are partially quatemized with diethyl sulfate (Polyquaternium 11) (142—144). They afford very hard, clear, lustrous, nonflaking films on the hair that are easily removed by shampooing. More recendy, copolymers with methyl vinyl imidazoliiim chloride (Polyquaternium 16) (145) or MAPTAC (methacrylamidopropyltrimethyl ammonium chloride) (Polyquaternium 28) have been introduced. Replacement of the ester group in DMAEMA with an amide analog as in Polyquaternium 28 results in a resin resistant to alkaline hydrolysis and hence greater utility in alkaline permanent-wave and bleach formulations (see Quaternary ammonium compounds). 

Quatemization of various pyridazinethiones and pyridazinyl sulfides is dependent on the substituents attached to the pyridazine ring. For example, 3-methylthiopyridazine and 6-methyl-3-methylthiopyridazine react with methyl iodide to form the corresponding 1-methyl-3-methylthio and l,6-dimethyl-3-methylthio derivatives (85). On the other hand, if a larger group, such as methoxy or phenyl, is attached at the 6-position, quaterniza-tion takes place at position 2 to give 6-substituted 2-methyl-3-methylthiopyridazines (86 Scheme 24). 

Imidazole, l-methyl-2,4,5-triphenyl-photochemical addition reactions, 4, 421 Imidazole, nitro-applications, 5, 498 IR spectra, 5, 358 mass spectra, 5, 359 quatemization, 5, 386 reactions, 5, 441 reduction, 5, 441 UV spectra, 5, 356 Imidazole, 1-nitro-reactions, 5, 454 Imidazole, 2-nitro-, S, 415 applications, 5, 498 reactions, 5, 96 reduction, 5, 441 synthesis, 5, 378, 395 Imidazole, 4-nitro-deuteration, 5, 417 methylation, 5, 383, 388, 389... 

Isoxazoline, 5-methyl-3-phenyl-quatemization, 6, 39 2-Isoxazoline, 3-nitro-... 

Pyrrolo[2,3-6]pyridine, 6-methyl-reaction with aldehydes, 4, 503 reaction with benzaldehyde, 4, 511 Pyrrolo[2,3-6]pyridine, 7-methyl-hydrogenation, 4, 508 Pyrrolo[2,3-6]pyridine, 3-nitro-2-phenyl-reduction, 4, 511 Pyrrolo[2,3-6]pyridine, 2-phenyl-nitrosation, 4, 506 quatemization, 4, 503 synthesis, 4, 522... 

UV spectra, 5, 798 synthesis, 5, 833 thermolysis, 5, 812 Tetrazole, 5-amino-2-methyl-methylation, 5, 818 Tetrazole, 2-aryl-5-substituted quatemization, 5, 815 Tetrazole, 5-aryl-acidity, 5, 816... 

Thiazole, 2-acetylamino-4-methyl-alkylation, 6, 256 Thiazole, 2-acylamino-4-hydroxy-synthesis, 6, 297 Thiazole, 5-alkoxy-cleavage, 6, 289 synthesis, 6, 302 Thiazole, 2-alkyl-A7-alkylation, 6, 253 hydrogen exchange, 6, 276 methylation, 6, 253 quatemization, 6, 253-254 reactions, S, 88 Thiazole, 4-alkyl-A7-alkylation, 6, 253 methylation, 6, 253 quatemization, 6, 253-254 Thiazole, 5-alkyl-A7-alkylation, 6, 253 methylation, 6, 253 Thiazole, 2-alkylamino-tautomerism, 6, 248 Thiazole, 4-alkyl-2,5-dimethyl-quatemization, 6, 253-254 Thiazole, 2-alkylthio-reactions, S, 103 rearrangement, 5, 103 6, 291 Thiazole, 3-allyl-4-hydroxy-2-imino-synthesis, 6, 297 Thiazole, 2-allyloxy-rearrangement, 6, 289 Thiazole, 2-amino-diazo coupling, 6, 257 nitration, 6, 255... 

The 3-pyridylcarboxamide, prepared from the anhydride (Pyr, 99% yield), is cleaved (55-86% yield) by basic hydrolysis (0.5 M NaOH, rt) after quatemization of the pyridine nitrogen with methyl iodide. ... 

Berg et al. defined a different ortho steric constant. The model reaction is the quatemization of substituted pyridines with methyl iodide in acetonitrile solution. 

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

Many heterocyclic halogen compounds are capable of quatemizing nitrogen bases and, indeed, of self-condensation, which can occur with great ease (for example, on warming a solution of l-chloro-4-methyl-... 

The action of methyl iodide on chloro-substituted heterocychcs usually results, in addition to quatemization, in the replacement of the chlorine by iodine if the halogen is in a position alpha or gamma to the quaternary center, particularly so in the former case. This type of replacement is less likely if dimethyl sulfate is used but may still occur to give a sulfate betaine (see Section IV, C). An easy method to obtain a-halogeno-quatemary salts has recently been discovered by Balli and Kersting who reacted the readily accessible triethyloxonium borofluoride 12 with a variety of bases. The very... 

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