Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• -inhibiting and antialgal properties [49], show anticancer activity [50][51], and are inhibitors of bacterial enzyme synthetase MurD with E. coli [52]. Additional treatment of thiazolidin-4-one 8 with a fivefold excess of hydrazine hydrate resulted in the formation of a 1H-pyrazole: A total of two hydrazine

• molecules were incorporated into the final product, whereas two additional equivalents were consumed capturing hydrochloric acid. In this way, the 1H-pyrazole 27 with an exceptional substitution pattern was obtained in 64% yield. The same reaction was applied to 5-arylmethylidene-thiazolidin-4-one 25 which

• furnished the corresponding 1H-pyrazole 28 in 52% yield (Scheme 5). A plausible multistep mechanism of this conversion is shown in Scheme 6: Initially, a first molecule of the strong nucleophile hydrazine is assumed to substitute the single C–Cl group within the trichlorovinyl subunit of 8 to give the

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• ). To further investigate the scope, a single case using allenic MBH alcohol 6 as the substrate was studied (Scheme 3). However, under similar conditions, the reaction between alcohol 6, tert-butyl azodicarboxylate (2c), and PPh3 afforded an interesting 1H-pyrazole compound 7 in 58% yield. A possible

• silica gel (gradient eluant: petroleum ether/ethyl acetate 9:1–3:1) to afford the hydrazines 3. Synthesis of 1H-pyrazole 7 Under N2 atmosphere and at room temperature, PPh3 (157 mg, 0.6 mmol) was slowly added to a stirred solution of allenic MBH alcohol 6 (61 mg, 0.3 mmol) and di-tert-butyl

• to column chromatography on silica gel (eluant: petroleum ether/ethyl acetate 9:1) to afford the 1H-pyrazole compound 7 in 73 mg, 58% yield, as slightly yellow oil. Synthesis of α-alkylidene-β-hydrazino acid derivatives from MBH adducts. Initial investigation. Synthesis of 1H-pyrazole 7. A plausible

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• are shown in Scheme 3. It is well known that the reaction of hydrazine hydrate with alkoxymethylidenemalononitrile affords 3-amino-1H-pyrazole-4-carbonitrile (5a) [8][9][10][11][12][13]. Eight tautomeric forms of 5a could theoretically be expected (Figure 1). Five of these tauromeric forms carry an

• numbering and the fourth and fifth numbers giving the positions of two hydrogens. When dimethyl methoxymethylidenemalonate (3b) is used, methyl 3-hydroxy-1H-pyrazole-4-carboxylate (5b) is formed. Analogously, reaction of diethyl ethoxymethylenemalonate (3c) gives the corresponding ethyl 3-hydroxy-1H

• NMR spectra of aminonitrile 5a showed one set of broad signals. The 13C chemical shifts of the pyrazole C-atoms (δ pyrazole C3(5) 154.1 ppm, δ pyrazole C-4 73.5 ppm, and δ of the quaternary pyrazole C5(3) 140.0 ppm) resemble those of ‘fixed’ N-methyl compound 5-amino-1-methyl-1H-pyrazole-4

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• 1/2 and comparison of 5 vs 6). The reaction conditions were compatible with a halogen substituent such as in 2e (Table 2, entries 7 and 8), which was obtained in up to 67% yield. Gratifyingly the presence of 4-substituted 1H-pyrazole allowed the clean formation of the corresponding difluoroadduct 2f

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• by Panke et al. [27]. The nitration product of 1-methyl-3-propyl-1H-pyrazole-5-carboxylic acid is an intermediate for the “life-style drug” Sildenafil® (Scheme 1). Similarly, nitration of 2-methylindole, pyridine N-oxide and toluene (also with an acetyl nitrate Ac2O/HNO3 mixture) were conducted. The

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• Materials, Polish Academy of Sciences, M. Curie-Skłodowskiej 34, Zabrze 41-819, Poland 10.3762/bjoc.9.173 Abstract A method for the synthesis of N-aryl-C-nitroazoles is presented. A coupling reaction between variously substituted arylboronic acids and 3(5)-nitro-1H-pyrazole catalyzed by copper salt has

• conditions on the yield of the product has been presented. Results and Discussion The group of products that we mainly describe is the 1-aryl derivatives of 3(5)-nitro-1H-pyrazole (1a). This is still a barely investigated group of compounds that can have attractive properties. Some recent reports describe

• ], and are described as being useful for the treatment of cognitive-deficit-associated psychiatric, neurodegenerative and neurological disorders [33]. Only four papers describe the synthesis of 3-nitro-1-phenyl-1H-pyrazole. It may be a product of oxidation of 3-amino-1-phenyl-1H-pyrazole [18], a product

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• simple and nonlaborious method to access dipyrazolo[1,5-a:4',3'-c]pyridines from easily obtainable 5-alkynyl-1-phenyl-1H-pyrazole-4-carbaldehydes through a silver triflate catalyzed one-pot tandem reaction with p-toluenesulfonyl hydrazide and an appropriate aldehyde or ketone. Moreover, the novel

• and 15N NMR (in bold) chemical shifts of 5d in CDCl3 solution (with numbering of ring atoms). Intermediate reactions of pyrazole-4-carbaldehyde 1a. Multicomponent reaction of various 5-alkynyl-1-phenyl-1H-pyrazole-4-carbaldehydes 1 with p-toluenesulfonyl hydrazide and aldehydes or ketones 4

Fluorescent hexaaryl- and hexa-heteroaryl[3]radialenes: Synthesis, structures, and properties

• Antonio Avellaneda,
• Courtney A. Hollis,
• Xin He and
• Christopher J. Sumby

Beilstein J. Org. Chem. 2012, 8, 71–80, doi:10.3762/bjoc.8.7

• deficient hexaaryl[3]radialene observed thus far, and studies of their electrochemical and photophysical properties. Results and Discussion The first new [3]radialene compound targeted was hexa(pyrazol-1-yl)[3]radialene. However, the required starting material, 1-[(1H-pyrazol-1-yl)methyl]-1H-pyrazole

Regioselectivity in the multicomponent reaction of 5-aminopyrazoles, cyclic 1,3-diketones and dimethylformamide dimethylacetal under controlled microwave heating

• Kamal Usef Sadek,
• Ramadan Ahmed Mekheimer,
• Tahany Mahmoud Mohamed,
• Moustafa Sherief Moustafa and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2012, 8, 18–24, doi:10.3762/bjoc.8.3

• triethylamine as base produces the more thermodynamically stable dihydropyridine (Hantzsch-type product). In addition, the nature of the catalyst plays an important role [20]. A one-pot three component reaction of 5-amino-1H-pyrazole-4-carbonitrile, dimedone and triethylorthoesters in toluene under reflux was

• recrystallized from EtOH to give a pure sample of 8 as orange crystals, 303 mg (88% yield); mp 255–256 °C; 1H NMR (400 MHz, DMSO-d6) δ 1.01 (s, 6H, 2 CH3), 2.40 (s, 2H, CH2), 3.26 (s, 2H, CH2), 7.24–7.85 (m, 6H, 5 Ph-H and CH-NH), 11.76 (s, 1H, NH), 12.59 (s, 1H, pyrazole NH); 13C NMR (100 MHz, DMSO-d6) δ 27.95

Efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles from 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes

• Yiwen Yang,
• Chunxiang Kuang,
• Hui Jin,
• Qing Yang and
• Zhongkui Zhang

Beilstein J. Org. Chem. 2011, 7, 1656–1662, doi:10.3762/bjoc.7.195

• -donating effects, relative to substrates 2, leading to higher yields. We also used 1-(2,2-dibromovinyl)-4-methylbenzene (2d) as a dipolarophile to react with 3-phenylsydnone. In the process, two isomers, 4-bromo-1-phenyl-3-p-tolyl-1H-pyrazole (3m) and 3-bromo-1-phenyl-4-p-tolyl-1H-pyrazole (3n) were found

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• then dried (MgSO4), filtered and the solvent evaporated to give a solid residue, which was purified by recrystallisation or column chromatography on silica gel to give the desired 4-fluoropyrazole product. 4-Fluoro-3,5-dimethyl-1H-pyrazole (4a) Pentane-2,4-dione (1a) (0.10 g, 1.0 mmol) in MeCN (4 mL, 2

• mL/h), fluorine (8 mL/min), and hydrazine hydrate (3a, 0.07 g, 1.5 mmol) in ethanol (4 mL, 2 mL/h), after purification by column chromatography on silica gel with hexane and ethyl acetate (1:1) as the eluent, gave 4-fluoro-3,5-dimethyl-1H-pyrazole (4a) (0.075 g, 66%) as pale yellow crystals; mp 107

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• hydrazine, on the other hand, led to 5-aryl-3-arylamino-1H-pyrazole-4-carbonitriles 36, instead of the 5-aminopyrazole 37, which can be rationalized in terms of the higher reactivity of the carbonyl group of 35 toward hydrazine compared to the cyano group (Scheme 9) [40]. Gao and Lam recently reported a

•  33). The reaction of cyanoacetylhydrazine (125) with α-bromoacetophenone (124) gave the N-[2-bromo-1-phenylethylidene]-2-cyanoacetohydrazide (126). Compound 126 readily underwent cyclization when treated with potassium cyanide to give 5-amino-1-cyanoacetyl-3-phenyl-1H-pyrazole (128) through the

• . Solid-support synthesis of 5-N-alkylamino and 5-N-arylaminopyrazoles. Synthesis of 5-amino-1-cyanoacetyl-3-phenyl-1H-pyrazole. Synthesis of 3-substituted 5-amino-1-aryl-4-(benzothiazol-2-yl)pyrazoles. Synthesis of 5-amino-4-carbethoxy-3-methyl-1-(4-sulfamoylphenyl)pyrazole. Synthesis of inhibitors of

Pd/C-mediated synthesis of α-pyrone fused with a five-membered nitrogen heteroaryl ring: A new route to pyrano[4,3-c]pyrazol-4(1H)-ones

• Dhilli Rao Gorja,
• Venkateswara Rao Batchu,
• Ashok Ettam and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 64, doi:10.3762/bjoc.5.64

• (Scheme 1). Results and Discussion The starting material required for our synthesis, 5-iodo-1-methyl-1H-pyrazole-4-carboxylic acid (1), was prepared from commercially available ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylate [20] (4) via a two-step process as shown in Scheme 2. Thus Sandmeyer type

• medicinal chemistry. Polycyclic azaheteroaromatics (A) and pyrano[4,3-c]pyrazol-4(1H)-ones (B). Pd/C-mediated synthesis of 6-substituted pyrano[4,3-c]pyrazol-4(1H)-ones 3. Preparation of 5-iodo-1-methyl-1H-pyrazole-4-carboxylic acid (1). Mechanism of ring closure of intermediate alkyne Z. Effect of reaction

• conditions on the Pd-catalyzed coupling of 5-iodo-1-methyl-1H-pyrazole-4-carboxylic acid (1) with 1-hexyne (2a).a Pd/C-mediated synthesis of 6-substituted pyrano[4,3-c]pyrazol-4(1H)-onesa (3). Supporting Information Supporting Information File 84: General procedure for the preparation of 3 and spectral data

An easy synthesis of 5-functionally substituted ethyl 4-amino- 1-aryl- pyrazolo- 3-carboxylates: interesting precursors to sildenafil analogues

• Said A. S. Ghozlan,
• Khadija O. Badahdah and
• Ismail A. Abdelhamid

Beilstein J. Org. Chem. 2007, 3, No. 15, doi:10.1186/1860-5397-3-15

• arylhydrazononitriles 1a-c are valuable precursors to 4-amino-5-substituted-1-aryl-1H-pyrazole-3-carboxylic acid ethyl ester which can be used for preparation of sildenafil analogues. synthesis of Ethyl 4-amino-5-substituted-1-aryl-1H-pyrazole-3-carboxylates (4) Reactivity of pyrazole 4b with phenylisothiocyanate and