Pyrazolones, condensation with aldehydes

In addition, condensation of pyrazolones 173a with aldehydes and subsequent cyclization of the resultant imines 173b gave the 4-substituted products 174 (R = Me, Ph).46 Under basic conditions, however, acetone and 173a cyclized spontaneously, giving the 4,4-dimethyl derivative 175.156... 

Pyrazolones also condense with aldehydes in aldol-type processes, or react with other electrophiles, such as carbon disulfide, in each case reaction presumably proceeding via the enol tautomer, or its anion. In basic solution isoxazol-3-ones alkylate either on oxygen or nitrogen, and the choice of base can influence the ratio. ... 

For instance, the pyrazolone 10 undergoes Knoeve nagel condensation (with aldehydes 9) and azo coupHng (with diazonium ions 11) at C-4, N-alkylation (e.g., with CH3I or (CH30)2S02 12) and O-alkylation (e g., with diazomethane - 13) ... 

Pyrazolones (154) and isoxazolones (155) can also be used in the Knoevenagel reaction. Thus condensations with aliphatic aldehydes, aromatic aldehydes and ketones in the presence of ethylenediammon-ium diacetate or other typical catalysts provide the corresponding alkylidene and benzylidene compounds in good yields (for stereochemistry see Section 1.1A new method involves the use of dicyclohexylcarbodiimide at 20 C without an additional catalyst. ... 

The catalysed alkylation of l//,4//-pyrazol-5-ones is solvent dependent. In benzene, bis-alkylation occurs at the 4-position whereas, in a carbon disulphide benzene mixture, O-alkylation is observed, although the major product (4, Scheme 5.22) results from nucleophilic attack by the pyrazolone on the carbon disulphide, followed by alkylation of the dithiolate dianion [92]. The catalysed reaction of 2-thiono-3-aryl-thiazolidin-4-ones with alkylating agents under soliddiquid two-phase conditions results in alkylation at the 5-position (60-80%) [93]. The aldol condensation of the thiazolidinones with aryl aldehydes is also catalysed by quaternary ammonium salts. 

An interesting entry to functionalized dihydropyrans has been intensively studied by Tietze in the 1990s using a three-component domino-Knoevenagel Hetero-Diels-Alder sequence. The overall transformation involves the transient formation of an activated heterodienophile by condensation of simple aldehydes with 1,3-dicarbonyls such as barbituric acids [127], Meldrum s acid [128], or activated carbonyls. In situ cycloaddition with electron-rich alkenes furnished the expected functionalized dihydropyrans. Two recent examples concern the reactivity of 1,4-benzoquinones and pyrazolones as 1,3-dicarbonyl equivalents under microwave irradiation. In the first case, a new three-component catalyst-free efficient one-pot transformation was proposed for the synthesis of pyrano-1,4-benzoquinone scaffolds [129]. In this synthetic method, 2,5-dihydroxy-3-undecyl-1,4-benzoquinone, paraformaldehyde, and alkenes were suspended in ethanol and placed under microwave irradiations to lead regioselectively the corresponding pyrano-l,4-benzoquinone derivatives (Scheme 38). The total regioselectivity was... 

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

Another variation of the Biginelh condensation involved the reaction of aldehyde 42, guanidine hydrochloride with various pyrazolones 41 to provide pyrazo-lopyrimidines 43 (Scheme 10) [30]. All the products obtained were tested against the M. tuberculosis H37 Rv strain and found to be active. In particular, compounds 44-46 had comparable activity (MIC =1.2 pg/mL) to first-Une drugs such as rifampicin (RIP) (MIC = 1 pg/mL). 

The derivatization of aldehydes in reducing carbohydrates can also be performed by a condensation reaction between the active hydrogens of l-phenyl-3-methyl-5-pyrazolone (PMP) and the aldehyde functionality under slightly basic condition. The formed bis-PMP derivatives can be separated by CZE and detected by UV absorbance. Oligosaccharides can also be separated as complexes with a variety of compounds, including acetate, molybdate, germanate, stannate, arsenite, wolfra-mate, vanadate, and tellurate of various alkali and alkaline... 

Condensation of 403 with aromatic aldehydes in the presence of ZnCl2 produced the corresponding 4-arylidenepyrazole derivatives 404 in 50-75% yield after 5-8 h heating at 140-150 °C. However, when the reaction was done under MWI for 5-7 min, the products were identified as l/f-pyrazolo[3,4-Z)]quinolines 405 and not 404 albeit in lower yields (40-71%) (Scheme 81) (00MI4). Reaction of 407 with pyrazolones 406 gave 408 (99SC4403). 

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