LINK SYNTHESIS WITH 3-HYDROXY-1H-PYRAZOLES - 3-CARBOXYISOALKYLOXY-1H-PYRAZOLES - BICYCLIC ACYLPYRAZOLIUM SALTS AND GAMMA-LACTAMS - 3-CARBOXYISOALKYLOXY-4,5-DIHYDRO-1H-PYRAZOL-5-ONES

1-Substituted 3-hydroxy-1H-pyrazoles 1 react with chloroform, NaOH, an d aceton rasp. butan-2-one O-regio-specifically to yield 2-methyl-2-[( 1H-pyrazol-3-yl)oxy]-propanoic resp. -butanoic acids 14 via a dichloro carbene (12)-dichlorooxirane (9) pathway. Chlorides 17 of 14 easily cy clize to N-acylpyrazolium salts 18/19, which quantitatively afford est ers 22-26 and amides 27-29 of 14. Enantiomers of the butanoic acid 14h , obtained via their diastereomeric cholesterol esters, differ in thei r stimulus to peroxisome proliferation. At 140 degrees C pyrazolium sa lts 18 undergo thermolysis to bicyclic beta-oxa-gamma-lactams 30-32. 3 -Carboxyisoalkylamino-pyrazoles similarly give 1H-beta-aza-gamma-lacta ms 34. Reactions of 14 with surplus SOCl2 result in 6-chloro- 37 resp. 7-chloro-beta-oxa-gamma-lactams 38 via chlorosulfinylation and extrus ion of SO, and in 4,4-bispyrazolyl-sulfoxide 39. A mild introduction o f additional O-functions into pyrazoles affording 4,5-dihydro-3-hydrox y-5-oxo-1H-pyrazoles 52-57 is presented. Biological effects of the new pyrazoles are protection against shock and ADP-induced thromboembolis m, reduction of serum lipids and improvement of blood flow.