Pyrazole quaternary salts

Pyrazoles and imidazoles carrying a substituent on nitrogen, as well as oxazoles, thiazoles, etc., are converted by alkyl halides into quaternary salts. This is Illustrated by the preparation of thiamine (89) from components (87) and (88). 

Amino and sulfur analogues of pyrazolones also yield the aromatic quaternary salt (231 X = NH or S). If the pyrazole bears a substituent with a second pyridine-like nitrogen atom, an intramolecular bridge can be formed by reaction with a dihalogenoalkane. Thus pyrazol-I -ylpyridines react with 1,2-dibromoethane to form (233) (81JHC9). 

Only AT-unsubstituted pyrazoles react, thus no 1,2-disubstituted quaternary salts can be obtained in that way. 

Dimethylaminopyrazoles react with alkylating agents to afford quaternary salts (72BSF2807). The nitrogen atom of the dimethylamino group is the most reactive in the case of 3-dimethylamino- and 4-dimethylamino-pyrazoles (formation of 456 and 457 salts, respectively) whereas 5-dimethylaminopyrazoles yield aminopyrazolium salts (458). 

Pyrazole, C-formyl-conformation, 5, 209 Pyrazole, fluoro-reactions, 5, 263, 267 Pyrazole, 4-fluoro-5-hydroxy-tautomerism, 5, 214 Pyrazole, 1-germyl-synthesis, 5, 236 Pyrazole, halo-halogenation by, 5, 54 reactions, 5, 104, 105, 266 reduction, S, 105, 106, 266 Pyrazole, 3-halo-1-phenyl-quaternary salts... 

Quaternary salt formation in a 1-substituted pyrazole ring (cf. 23) can occur only at N-2 to give the fully resonance-stabilized symmetrical salt 24. This reaction, which proceeds very readily, has been known for many years and therefore will not be commented on here. 

Two ring systems derived from pyrazole have been studied more recently. The 4 -pyrazole ring (25) forms quaternary salts (26) with fair ease, and, as in the case of pyridazine (see Section IV, C), the direction of quatemization is controlled by the nature of R and... 

Reaction of the quaternized salts of 4-ethoxycarbonyl-3,5-dimethyl-f-phenylpyttolo(furo or thieno)[2,3-c]pyrazole 34 with the iodomethane quaternary salts of pyridine, quinoline, and isoquinoline in ethanol with catalytic piperidine gave 3-[4(f)]-monomethine cyanine dyes (e.g., 35). Additionally, 3-[2(4)]-trimethine cyanine dyes and 4-[2(4)]-di-3[2(4)]-tri-mixed methine cyanine dyes (e.g., 36 and 37, respectively) were similarly prepared from the intermediates derived by reaction of 34 with triethyl orthoformate in the presence of piperidine (Scheme 8) <2002CCS106f>. 

In quaternary pyrazole salts, halogen substituents are noticeably activated the positive charge being spread over the whole ring naturally facilitates nucleophilic attack and hence increases the lability of the halogen. 872 Concerning quaternary salts of amino-pyrazoles, see Kudryashova.673,674... 

Pyrolysis of the quaternary salts of pyrazoles causes loss of alkyl halide and reformation of N-substituted pyrazoles. If the substituents in the 3- and 5-positions are similar in character, as well as those on the two nitrogen atoms, then the two possible products will be formed in comparable quantities.81 83,152, 412 711... 

By contrast, 3-hydrazino-l,2,4-thiadiazoles (163), which are prepared by ring closure methods, are very sensitive to acids and undergo elimination of sulfur with formation of 5-arylamino-l,2,4-triazoles (164) as indicated in Scheme 61 (63JCS4566). The mechanism of this conversion is not known but presumably involves the attack of a hard nucleophile at the 5-position followed by ring opening, loss of sulfur and recyclization as has been observed with the quaternary salts (77JCS(P1)1791) (see Schemes 22, 23, and 24). Hydrazine (163) reacts with aldehydes to produce hydrazones (165) and with dimethyl malonate to yield pyrazoles (166). Diazonium salts of type (153) have been prepared by the methods... 

Dequatemization of azolium quaternary salts initially involved pyrazol-ium compounds, which could be pyrolyzed in vacuum at ca. 200°C (66AHC417). The use of thiophenolate anion under phase transfer catalysis proved to be an excellent method of obtaining pyrazoles and indazoles in high yield from their corresponding quaternary salts [78CR(C)439]. The thermal descomposition of imidazolium quaternary salts has been studied by Grimmett et al. (77AJC2005). 

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