Pyrazolin-5-one derivatives

Irradiation of 4-hydroxy- and 4-alkoxy-3-pyrazolin-5-one derivatives (163 R = OH, OR) leads to ring cleavage with the formation of /3-diamides (165) 69TL271). The methylene blue sensitized rearrangement of the same pyrazolinone (R = H) to the oxindole (166) also... 

Muzolimine (710), a 1-substituted 2-pyrazolin-5-one derivative, is a highly active diuretic, differing from the structures of other diuretics since it contains neither a sulfonamide nor a carboxyl group. It has a saluretic effect similar to furosemide and acts in the proximal tubule and in the medullary portion of the ascending limb of the loop of Henle. Pharmacokinetic studies in dogs, healthy volunteers and in patients with renal insufficiency show that the compound is readily absorbed after oral administration (B-80MI40406). 

Purpuric acid lb 174 Pyrazolidine derivatives la 426 3,5-Pyrazolidindione derivatives lb 20 Pyrazolinone derivatives lb 277 Pyrazolin-5-one derivatives lb 327,329 Pyrazone lb 332 Pyrene lb 379 PyrethrinI lb 18 Pyrethrin II lb 18 Pyrethroids lb 86,87 Pyrethroid insecticides la 359 Pyridine alkaloids la 66 lb 279 Pyridine derivatives lb 119,244 Pyridinium carbinols lb 65 Pyridinium glycols lb 65 Pyridoxal la 157,158,253 Pyridoxamine la 253 Pyridoxine la 253... 

A facile synthesis of allenic esters (187) is by reaction between acid chlorides (185) and phosphoranes (186) derived from a-halo-esters. Yields are 10— 70% presumably ketens are intermediates. Cyclic /3-keto-esters can serve as precursors to cyclic allenic esters by sequential conversion to the 2-pyrazolin-5-one derivatives, using hydrazine and oxidation with thallium trinitrate (Scheme 26) overall yields are around 50%. ... 

The IR spectrum of CuL-4H20, where H2L = 2-amino-4-methylthiazole-dipropionic acid, is consistent with 1 coordination through amine N and two carboxylate O atoms.IR ligand bands for Cu(o-haph)2L2, where o-haph = o-hydroxyacetophenone, L = range of 2- or 3-pyrazoline-5-one derivatives, show that L is coordinated via O or N+O atoms. 

A second common reaction of sulphonium ylides is Michael addition to ajS-unsaturated carbonyl compounds, giving cyclopropanes. This reaction forms the basis of a cyclopentene synthesis starting from sulphonium allylide (14). Other recent examples include the preparation of spiro[cyclopropane-l,4-A -pyrazolin]-5 -one derivatives (15) and cyclopropyl-ulose (16). Un-... 

Pyrazolones. The 0x0 derivatives of pyrazolines, known as pyrazolones, are best classified as follows 5-pyrazolone, also called 2-pyrazolin-5-one [137-44-0] (36) 4-pyrazolone, also called 2-pyrazolin-4-one [27662-65-3] (37) and 3-pyrazolone, also called 3-pyrazolin-5-one [137-45-1] (38). Within each class of pyrazolones many tautomeric forms are possible for simplicity only one form is shown. 

The reaction is very common in pyrazolone chemistry. Since alkoxypyrazoles and tautomerizable pyrazolones undergo this reaction and 3-pyrazolin-5-ones, like antipyrine, do not, it is assumed that the reaction takes place at C-4 of the OH tautomer. Pyrazolone diazo coupling is an important industrial reaction since the resulting azo derivatives are used as dyestuffs. For instance, tartrazine (Section 4.04.4.1.3) has been prepared this way. 3,5-Pyrazolidinediones react with aryldiazonium salts resulting in the introduction of a 4-arylazo group. As has been described in Section 4.04.2.1.4(v), diazonium salts couple in the 3-position with indazole to give azo compounds. 

Pyrazolones show a great variety of reactions with carbonyl compounds (B-76MI40402). For instance, antipyrine is 4-hydroxymethylated by formaldehyde and it also undergoes the Mannich reaction. Tautomerizable 2-pyrazolin-5-ones react with aldehydes to yield compound (324) and with acetone to form 4-isopropylidene derivatives or dimers (Scheme 8 Section 4.02.1.4.10). 

A-Oxidation with peracids (Section 4.04.2.1.3) and the transformation of pyrazoles into 4,4-dihalogeno-2-pyrazolin-5-ones (Section 4.04.2.1.4(v)) have already been discussed. Transformation of non-aromatic 2-pyrazolin-5-ones into the 4-oxo derivatives will be examined in Section 4.04.2.2.l(ii). 

The linking methine chain includes an even number of methine groups (0,2,4). They are commonly named as derivatives of the ketomethylene ring, for example, 3-ethyl-5-(3-ethyl-4,5-diphenylthiazolin-2-ylidene)-rhodanine (5) and 4-[4-(3-methyl-4,5-diphenylthiazolin-2-ylidene)-2-butenylidene]-3-methyl-l-p-sulfophenyl-2-pyrazolin-5-one (6) (Scheme 4). 

A variety of heterocyclic systems have been used for forming merocyanines. The more usual nitrogen-containing heterocycles involved include benzimidazole, quinoline, ben-zothiazole, benzoselenazole, thiazole, thiazoline and indolenine. Among the more useful carbonyl-containing heterocycles are derivatives of 2-pyrazolin-5-one, 2-thiobarbituric acid, rhodanine and hydantoin. 

Certain dyes derived from somep-phenylenediamines satisfy the requirements of practical image dyes. For example, the developer of Scheme 5 gives yellow and magenta azamethine dyes, respectively, with benzoylacetanilides and 2-pyrazolin-5-ones as couplers, and cyan indoaniline dyes result from phenols and naphthols. 

The cyan dye (71) (52USP2612448) and the yellow dye (72) (62GEP1137626), both derived from 2-pyrazolin-5-ones, have been suggested for use in dye bleach materials. 

Condensation with Carbonyl Groups The hydrogen atom at the 4-position is sufficiently activated for 5-hydroxypyrazoles (pyrazolin-5-ones) to undergo condensation with ketones in acid media to yield 4-alkylidenepyrazolin-5-ones (61) in alkali, dipyrazolinonylmethane (62) derivatives are formed.644,645... 

The 5-hydrazino-l,2,4-thiadiazoles (152) are stable in acid and base and readily form hydrazone derivatives on reaction with suitable carbonyl compounds. Thus, (152 R = Me, Ph, m-02NC6H4) reacts with /3-keto esters to form 3-alkyl-l-(l,2,4-thiadiazol-5-yl)pyrazolin-5-ones (161) which undergo coupling with p-nitrosodialkylanilines to form azomethine dyes (162) (65AHC(5)119>. 

Reaction of 4-chloro-2-pyrazolin-5-ones with potassium carbonate proceeds along two pathways, leading to diketo derivatives of pyrazoIo[l,2-a]pyrazoIe (syn- and anti- dioxabimanes )- A mechanism involving the intermediate formation of diazacyclopen-tadienone (185) which reacts with its potential extended diazoalkane functionality in dipolar cycloaddition fashion to give syn-dioxabimanes (major product) and anri-dioxabimanes (minor product) has been proposed (Scheme 6) (80JA4983). 

Solid-phase synthesis of substituted pyrazolones 550 from polymer-bound /3-keto esters 549 has been described (Scheme 68) <2001EJ01631>. Trisubstituted pyrazole carboxylic acids were prepared by reaction of polymer-bound arylidene- or alkylidene-/3-oxo esters with phenylhydrazines <1999S1961>. 2-(Pyrazol-l-yl)pyrimi-dine derivatives were prepared by cyclocondensation of ethyl acetoacetate and (6-methyl-4-oxo-3,4-dihydropyrimi-din-2-yl)hydrazine with aromatic aldehydes <2004RJC423>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted-pyrazolin-5-ones <2002T3639>. Reactions of hydrazines with A -acetoacetyl derivatives of (45 )-4-benzyloxazolidin-2-one (Evans oxazolidinone) and (2R)-bornane-10,2-sultam (Oppolzer sultam) in very acidic media gave pyrazoles retaining the 3(5)-chiral moiety <1999S157>. 

---