Triazoles, acidity

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

Stilben-4-yl)naphthotriazoles (2) are prepared by diazotization of 4-amino-stilbene-2-sulfonic acid or 4-amino-2-cyano-4 -chlorostilbene, coupling with an ortho-coupling naphthylamine derivative, and finally, oxidation to the triazole. 

BAS 111 l-Phenoxy-3-(lH-l,2,4-tria2ole-l-yl)-4-hydroxy-5,5-dimethylhexane [9003-11-6] (BAS 111) (46) is a triazole that has plant growth inhibiting properties. It exerts its influence by inhibiting the production of gibbereUic acid in plants this has been demonstrated in canola (31,37). 

Most of the GA-synthesis inhibitors characterized so far affect two segments of the compHcated pathway from MVA to the many different GAs identified. The cycHzation reactions that produce / Akaurene are inhibited by the onium growth retardants, and the oxidations of /-kaurene to /-kaurenoic acid are sensitive to heterocycHc triazoles such as paclobutrazol and similar compounds. Other enzymes in the pathway are points for pathway dismption by as yet undeveloped GA biosynthesis inhibitors (236). 

Nitric acid may be precipitated by nitron [2218-94-2] (4,5-dihydro-l,4-diphenyl-3,5-phenylimino-l,2,4-triazole). The yellow precipitate maybe seen at dilutions as low as 1 60,000 at 25°C or 1 80,000 at 0°C. To prevent nitrous acid from interfering with the test results, it may be removed by treating the solution with hydrazine sulfate, sodium azide, or sulfamic acid. 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Ring substituents can have a considerable effect on the acidity of the system. In the 1,2,4-triazole series a 3-amino group decreases the acidity to 11.1, a 3-methyl group to 10.7, whereas a 3-phenyl group Increases the acidity to 9.6, and 3,5-dlchloro substitution to 5.2 (71PMH(3)1). 

Amination at an azole ring nitrogen is known for Af-unsubstituted azoles. Thus 4,5-diphenyl-1,2,3-triazole with hydroxylamine-O-sulfonic acid gives approximately equal amounts of the 1- (104) and 2-amino derivatives (105) (74AHC(16)33). Pyrazole affords (106) and indazole gives comparable amounts of the 1- and 2-amino derivatives. 

Imidazoles and benzimidazoles (155) react with acid chloride and alkali to give compounds of type (157), but these are reactions of the cation (156). 1,2,4-Triazoles and tetrazoles similarly undergo ring opening. 

TV-Amino groups are replaced by hydrogen on treatment with nitrous acid (e.g. 562 -> 563) (80AHC(27)24l) or phosphorus trichloride (l,2,4-triazole-4-acylimines are converted into triazoles (74AHC(17)213)). 

In the indazole series an example of a type (c) reaction (Figure 25) has been described utilizing a 1,3-dipole instead of a diene (Scheme 32) (76H(4)1655). The cycloadduct (351) is transformed into the triazole (352) on reaction with hydrochloric acid. 

Triazole-l-carboxylic acid, 4-aryloxy-, ethyl ester... 

Triazole-4-carboxylic acid, 5-chloro-1-phenyl-UV, 5, 685 (55JA6532)... 

Triazole-4,5-dicarboxylic acid, 2-(tributylstannyl)-, diethyl ester... 

Pyrazolino[2,3-c][l,2,3]triazoles, 5, 702 Pyrazolium hydroxide, l,2-dimethyl-3,5-diphenylanhydro-4-hydroxy-IR spectra, 5, 201 Pyrazolium salts dequatemization, 5, 269 H NMR, 5, 185 hydrogen exchange at ring carbon, 5, 245 mesoionic compounds, 5, 171 nitrodebromination, 5, 237 reactivity, 5, 217 reduction, 5, 68, 243 synthesis, 5, 156 UV spectra, 5, 199 Pyrazolium salts, amino-reactions, 5, 262 Pyrazolium salts, bromo-nucleophilic displacements, 5, 266 Pyrazolium salts, 1,2-dimethyl-deuteration, 5, 175, 245 hydrogen exchange, 5, 71 acid-catalyzed, 5, 239 reactions... 

Pyrazolo[3,2-c][l,2,4]triazole-7-carboxylic acid synthesis, 6, 1018 Pyrazolotriazoles dye releasers... 

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