5-Pyrazolones esters

Phenylhydrazine condenses with acetoacetic ester to give a pyrazolone derivative which on methylation gives phenazone. The sulphonic acid similarly gives rise to the tartrazine dyestuffs. It is used to make indole derivatives by the Fischer process. 

P Keto esters (t.g., ethyl ocetoacetate) are soluble in solutions of caustic alkalis but not in sodium carbonate solution. They give colours with freshly prepared ferric chloride solution a little alcohol should be added to bring the ester into solution. Sodium ethoxide solution reacts to yield sodio compounds, which usually crystallise out in the cold. Phenylhydrazine yields pyrazolones. They are hydrolysed by boiling sulphuric acid to the Corresponding ketones, which can be identified as usual (Section 111,74). 

Some active 5-pyrazolone derivatives (707) and (708) in which the 1-phenyl substituent of antipyrine was replaced by 2 -, 3 - and 4 -pyridyl groups have been prepared (66HCA272). A series of aminoesters substituted at the nitrogen atom of the ester grouping with an antipyryl residue (709) were found to possess local anesthetic properties (69MI40400). 

One year later, Tietze and co-workers (97BMC1303) presented a general and straightforward method for the synthesis of diverse polymer-bound -keto esters starting from acid chlorides and Meldrum s acid. One such resin-bound y3-keto ester, 43, was treated with hydrazine hydrate in THF to afford resin-ffee N-2-unsubstituted pyrazolone 44 in 84% yield (Scheme 13). In the same paper, the synthesis of a large number of 4,5-disubstituted 2-phenyl-2,4-dihydro-37/-pyrazol-3-ones was reported. 

Osazones are particularly important in carbohydrate chemistry. In contrast to this behavior, P-diketones and P-keto esters give pyrazoles and pyrazolones, respectively (illustrated for P-keto esters) ... 

The recently reported (757) conversion of 5-pyrazolones directly to a,j8-acetylenic esters by treatment with TTN in methanol appears to be an example of thallation of a heterocyclic enamine the suggested mechanism involves initial electrophilic thallation of the 3-pyrazolin-5-one tautomer of the 5-pyrazolone to give an intermediate organothallium compound which undergoes a subsequent oxidation by a second equivalent of TTN to give a diazacyclopentadienone. Solvolysis by methanol, with concomitant elimination of nitrogen and thallium(I), yields the a,)S-acetylenic ester in excellent (78-95%) yield (Scheme 35). Since 5-pyrazolones may be prepared in quantitative yield by the reaction of /3-keto esters with hydrazine (168), this conversion represents in a formal sense the dehydration of /3-keto esters. In fact, the direct conversion of /3-keto esters to a,jS-acetylenic esters without isolation of the intermediate 5-pyrazolones can be achieved by treatment in methanol solution first with hydrazine and then with TTN. 

Under the same reaction conditions, -keto esters which have been alkylated on the a-carbon atom (thus leading to 3,4-disubstituted 5-pyrazolones upon treatment with hydrazine) give allenic esters in good (50-70%) yield (158). The mechanism (Scheme 36) again appears to involve thallation of the enamine tautomer of the 5 -pyrazolone, but deprotonation now takes place... 

Heating of P-keto esters or of 1 3-diketones with an equivalent amount of phenylhydrazine often yields substituted pyrazolones or p3u-azoles respectively. The latter may serve as derivatives of enols. 

Methods of synthesizing pyrazolone focus especially on ring closure by reaction of acetoacetic ester with phenyl or p-tolylhydrazine, affording water and ethanol as by-products. 

The reaction of pyrazolones (207) with 3-oxo-esters gives mainly the pyrazolo[l,2-a]pyrazol-l,5-(lff,5//) diones (208). However, with 207 (R = Ph), only oxazines 209 are obtained. Thermal and photochemical isomerization of 204 gives 209 (84CPB930, 84JAP59128384). Phenace-tylpyrazole (210) is cyclized to 211 with thiophosgene (84JOC3672). 

Reaction between hydrazines and p-diketones or P-keto esters (pyra-zoles pyrazolones)... 

Phenyl-3-methyl-5-pyrazolone, 998 p-Phenylpl lenacy 1 bromide, 962 p-Phenylphenacyl esters, 363 Phenylpropiolic acid, 755, 776 Phenylpropionaldehyde, 906, 907 Phenyl propionate, 676... 

Pyrolysis of the pyrazoline butanoic acid esters 258 gave the lactams 259 (R = H, C02Et).210 Pyrazolone 260 reacted with 2,3-dimethyl-1,3-butadiene to furnish the expected cycloadduct.211... 

The reactions of cinnamic acid derivatives with hydrazine are also in accord (56) with the above findings. The hydrazide 182 cannot, even at 200°C, be converted into the pyrazolone 185 (5-Endo-Trig process). However, the ester... 

Phenyl-5-Pyrazolones as Coupling Components. Especially lightfast yellow shades are obtained by using l-phenyl-5-pyrazolone coupling components. The first representative of the class to appear was Tartrazine, C.I. Acid Yellow 23, 19140 [1934-21-0], which is prepared today from l-(phenyl-4 -sulfonic acid)-3-car-boxy-5-pyrazolone as the starting compound, obtained from oxaloacetic ester and phenylhydrazine-4-sulfonic acid and coupling with diazotized sulfanilic acid. 

C.I. Acid Yellow 76, 18850 [6359-88-2] (14), is obtained by coupling diazotized 4-aminophenol onto the pyrazolone component and then esterifying with -toluene-sulfonic acid chloride in an alkaline medium. The toluenesulfonic ester group substantially improves the fastness to milling and makes the shade obtained largely independent of pH the lightfastness is not quite as good as that of C.I. Acid Yellow 17. 

Reaction of phenylhydrazine with the /J-keto ester (64) gives the pyrazolone (65).55 The hydantoin (66) has been obtained by the action of potassium cyanide and ammonium carbonate on ferrocenecarbox-aldehyde.67-69 The potentiometric titration64 of hydantoin (67) has been reported. 

Simple and complex hydrazides, with the general formula RCONHNHCOR, were readily dehydrogenated by DIB to the corresponding azo compounds, some of which were used as dienophiles for in situ Diels-Alder reactions [65,66]. Hydrazine itself in the form of its hydrate was similarly converted into diimide, NH — NH, which served for some in situ hydrogenations [67], Further reactivity accompanied by solvent participation was observed in some cyclic derivatives of hydrazine, i.e. pyrazolones. At low temperature these underwent ffagmentive loss of dinitrogen to give either methyl alkynoates or allenic esters [68] ... 

Pyrazole (3 chloro,4 carboxy,1 methyl 5 sulfonamide) halosulfuron Pyrazole (1.4 dimethyl,2 chloro, 3 formyl) fenpyroximate Pyrazole (2 methyl, 3 amino, 4 carboxy) pyrazosulfuron Pyrazole (2 methyl,4 carboxy, ethyl ester) pyrazosulfuron Pyrazole (1 methyl,2 ethyl,4 chloro 5 carboxy) tebufenpyrad 5 Pyrazolone (1.3 dimethyl) benzofenap, pyrazolinate, pyrazoxyfen Pyridazine (1 phenyl 3 hydroxy, 6 oxo) pyridafenthion... 

This reaction was extended to other (i-dicarbonyl compounds containing a nitro group [474 176], The mechanism of the reaction of hydrazine with 1,3-dicarbonyl compounds is still largely unclear. Nevertheless, important evidence was obtained to indicate that a dihydroxypyrazolidine intermediate is formed in this reaction [477], If hydroxylamine is used instead of free hydrazine in the reaction with nitromalonaldehyde, the product is 4-nitroisoxazole [471], When a mixture of nitrocyanoacetic ester with one equivalent of hydrazine hydrate and a small amount of water is boiled, 5-amino-4-nitro-3-pyrazolone is formed [478],... 

Polar yellow 5G is prepared by condensing p-chloro-m-sulfophenylhydrazine with acetoacetic ester, and coupling the resulting pyrazolone with diazotized p-aminophenol in acetic acid solution. The alkali sensitive dye which is formed is treated at 70°C. with p-toluenesulfonyl chloride, in the presence of soda and 1 mole of sodium hydroxide, to esterify the hydroxyl group. This esterification makes the dye insensitive to alkali and, at the same time, fast to milling on wool. 

This is the simplest member of the pyrazolone dyes which are prepared in two ways (a) from dihydroxytartaric acid and phenylhy-drazine (tartrazines), and (b) from phenylmethylpyrazolones by coupling with diazo compounds. The second method is simpler and has largely displaced the older, first method. The pyrazolone is prepared from a given phenylhydrazine (e.g., phenylhydrazinesulfonic acid, page 128) and acetoacetic ester, and coupled with diazotized aniline ... 

By heating the pyrazolone formed by the addition of d azoacetic ester to itaconic ester a tribasic cyclopropane acid of the following formula results OHa - 0.- CHs-COOH. No X / COQH UH-COCH... 

Benzoylhydrazine reacts with ethyl acetoacetate at 130 °C in the absence of solvent to give first the pyrazolone (295 R = PhCO). Water from the reaction hydrolyzes the benzoyl group and a second molecule of the ester reacts to give the pyranopyrazolone (296) (63BSF2742). The aminopyrazolones (297) and carbon disulfide give the zwitterionic pyrazolothiazines (298) which S,5-dialkylate with diazomethane or alkyl iodides (78FES799). 

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