Azolinones, acidity

Azolines 13C NMR, 5, 20 H NMR, 5, 17 NMR, 5, 14 Azolinethiones reactions, 5, 102-103 Azolinones acidity, 5, 72 13C NMR, 5, 16, 19 H NMR, 5, 14, 15 halogenation, 5, 58 hydrolysis, 5, 64 IR spectra, 5, 24, 27 reactions, 5, 81 with aldehydes, 5, 60 with ketones, 5, 60 Azolin-2-ones electrophilic attack, 5, 99 Azolium cations nucleophilic attack at carbon, 5, 61 reactivity, 5, 42 Azolium ions reactions with alkali, 5, 63 with amines, 5, 65 Azolium salts hydrogen exchange, 5, 70 nucleophilic attack at hydrogen, 5, 69-72 reactions... 

Aldehydes and ketones react with azolinones. The reaction between aldehydes and 2-phenyl-5-oxazolinone (131 Y = H), formed in situ from PhC0NHCH2C02H and AC2O, gives azlactones (131 Y = RCH). Similar reactions are given by 4-thiazolidinones, e.g. (132) gives (133) (79AHC(25)83), and 4-imidazolinones. In pyrazolin-5-ones the 4-position is sufficiently activated for condensation to occur with ketones in acidic media (Scheme 8) (66AH06)347). 

Azolinones are weak to medium strong acids of pK 4-11. They form mesomeric anions which react very readily with electrophilic reagents at the nitrogen, oxygen or carbon atoms, depending on the conditions see Section 4.02.1.1.4. 

Azolinones are protonated on oxygen in strongly acidic media. O-Alkylation of 2-azolinones can be effected with diazomethane thiazolinone (486) forms (487). Frequently O- and iV-alkylation occur together, especially in basic media where proton loss gives an ambident anion. 

Pyrazoles, isoxazoles and isothiazoles with a hydroxyl group in the 3-position (491 Z = NR, O, S) could isomerize to 3-azolinones (492). However, these compounds behave as true hydroxy derivatives and show phenolic properties. They give an intense violet color with iron(III) chloride and form a salt (493) with sodium hydroxide which can be O-alkylated by alkyl halides (to give 494 R = alkyl) and acylated by acid chlorides (to give 494 R = acyl). 

Azolinones. Although imidazolinones are usually resistant to hydrolysis, oxazolinone rings are often easily opened. In acid-catalyzed reactions of this type, water converts azlactones 262 into -acylamino-,-unsaturated acids 263. 1,3,4-Oxadiazolinones are readily opened by hot water to give hydrazine carboxylic acids, which undergo decarboxylation. 

Binz and Rath reported in 1931 that nitration of the pyrido[2,l-i>]quin-azolinone 286 with 30% nitric acid in concentrated sulfuric acid at 30 Cgave the 2-nitropyrido[2,l- )]quinazoline 218, whereas with 67% nitric acid in concentrated sulfuric acid at 50°C the 2,8-dinitro derivative 372 (R = H) was obtained. (The structures originally suggested for the products were not correct.)... 

Introduction of the sulfonyl group as an electrophile is in the carbocyclic ring. 4(3//)-Quin-azolinone is sulfonated in the 6-position by chlorosulfonic acid <60JA273i>. 

When an anthranilic acid ester is heated with ammonium thiocyanate, 2-thioxo-4(3//)-quin-azolinones (629) are formed. When alkyl- or aryl-isothiocyanates are used, the corresponding N3-substituted 2-thioxo-4-quinazolinones (629) are formed . 

The intensive chemical synthesis program on the pyridylimid-azolinone herbicides at the Agricultural Research Division of American Cyanamid resulted in the discovery of several important crop protection products (1-7). Among them are 2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid 1 (AC 243,997, imazapyr) and its isopropylamine salt 2 (AC 252,925) registered by American Cyanamid as ARSENAL, ASSAULT and CHOPPER total vegetation control herbicides. 

In later publications, however, the same authors reported that the reaction of bis(5(4H)oxazolinones) derived from naturally occurring a-amino acids, that is, with at least one hydrogen atom at the 4 position, with amine-terminated polyethers and polyamides in the bulk at 175-200 °C is also possible. Scheme 12 shows the synthesis in which the bisox-azolinones derived from alanine, valine, phenylalanine, and methionine were obtained. 

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