Regioselectivity of 1,3-dipolar cycloaddition reactions of C-acetyl-N-arylnitrilimines with acrylic acid derivatives and .alpha.,.beta.-unsaturated ketones (original) (raw)
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Acta Chimica Slovenica, 2009
1,3-Dipolar cycloadditions of racemic (1Z,4R*,5R*)-arylmethylidene-4-benzamido-5-phenyl-3-pyrazolidinon-1-azomethine imines 3 to enantiopure di-(-)-menthyl maleate (4) afforded mixtures of diastereomeric cycloadducts 5/5'-7/7'. Selectivity as well as stereochemistry of cycloadditions were dependent on the substituents at the 1'-Ar residue of dipoles 3. Thus, reactions of dipoles 3a-j with at least one free ortho-position gave either di-(-)-menthyl (1R*,2S*,3R*,5R*,6R*)-3-aryl-6-benzamido-7-oxo-5-phenylhexahydropyrazolo[1,2-a]pyrazole-1,2-dicarboxylates 5/5' (the endo-isomers) and/or di-(-)-menthyl (1S*,2R*,3R*,5R*,6R*)-3-aryl-6-benzamido-7-oxo-5-phenylhexahydropyrazolo[1,2-a]pyrazole-1,2-dicarboxylates 6/6' (the exo-isomers) with syn-oriented 3-H and 5-H, whilst reactions of 4 with ortho-disubstituted dipoles 3k,l gave (1S*,2R*,3S*,5R*,6R*)-diastereomers 7/7'k,l with anti-oriented 3-H and 5-H. Separation of diastereomeric cycloadducts 5/5'-7/7' by crystallization and/or MPLC furnished isomerically pure compounds 5a,b,d,g, 5'b,d,h, 6c,d,j, and 6'c,d,f and purified mixtures of diastereomers 5/5'e, 6/6'e,h, and 7/7'k,l in 1-42% yields. The relative configuration of the pyrazolo[1,2-a]pyrazolone structural element in the products 5/5'-7/7' was determined by NMR.
Arabian Journal of Chemistry, 2014
Dimethyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one 3 was prepared by an intramolecular cyclization of N-(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl) acetamide 2 in ethanol in the presence of piperidine. N-allylation and N-propargyl alkylation of N-substituted pyrazolo[3,4-d] pyrimidin-4(5H)-one 3 yielded the corresponding dipolarophiles 4 and 5 which afford by condensation with arylnitrile oxides in toluene the expected new isoxazolines 6 and isoxazoles 7, respectively. On the other hand, the aminopyrazole 1 in refluxing with ethanol in the presence of sodium hydroxide afforded the corresponding carboxamide 8, which then, was converted to its ethyl 3-methyl-4-oxo-1-phenyl-4,5-dihydro-1H-pyrazolo[3,4-d] pyrimidine-6carboxylate 9 with neat diethyl oxalate. The dipolarophile 10 on regiospecific 1,3-dipolar cycloaddition with arylnitrile oxides affords isoxazoles 11 and the unexpected deethoxycarbonylated isoxazoles 12. The target compounds were completely characterized by 1 H NMR, 13 C NMR, IR and HRMS.
Helvetica Chimica Acta, 1998
5S)-1-Benzoyl-3-[(E)-cyanomethylidene]-5-(methoxycarbonyl)pyrrolidin-2-one (5) was prepared in four steps from l-pyroglutamic acid (1). 1,3-Dipolar cycloadditions of diazomethane (6) and 2,4,6-trimethoxybenzonitrile oxide (7) gave substituted 1,2,7-triazaspiro[4.4]non-1-en-6-one 12 and 1-oxa-2,7-diazaspiro[4,4]non-1en-6-one 13 in 38 and 20% de, respectively. On the other hand, reaction of 5 with N-phenylbenzonitrile imines 8 and 9, generated in situ from the corresponding hydrazonoyl chlorides 10 and 11, respectively, and Et 3 N, furnished racemic pyrrolo [3,4-c]pyrazoles 14 and 15 in 61 and 56% de, respectively. Cycloaddition of nitrile oxide 7, when performed in the presence of Et 3 N, led to pyrrolo [3,4-d]isoxazole 16 in 85% de.
Synthesis and antimicrobial activity of pyrazolo [3, 4-b] quinolines containing pyrimidine moiety
Indian Journal of …, 2011
2-Amino-pyridine-3-carboxaldehyde and 3-cyclopropyl-3oxopropionic acid ethyl ester react each other to provide 2-cyclopropyl-[1,8]-naphthyridin-3-carboxylic acid ethylester (1) which reacts with 99 % hydrazine hydrate to yield 2-cyclopropyl-[1,8]-naphthyridine-3carboxylic acid hydrazide (2). This acid hydrazide (2), reacts with different acetophenones to yield respective Schiff bases (3a-h). Compounds 3a-h react with Vilsmeier-Haack reagent (DMF/POCl3) to furnish 1-(2cyclopropyl-[1,8]-naphthyridine-3-carbonyl)-3-phenyl-1H-pyrazole-4carbaldehydes (4a-h). 2-Cyclopropyl-[1,8]-naphthyridine-3-carboxylic acid hydrazide (2) on reaction with substituted acetylacetones and substituted ethyl acetoacetates gives substituted 2-cyclopropyl-[1,8]naphthyridin-3-yl)-(3,5-dimethyl-pyrazol-1-yl)-methanones (5a-d) and 2-(2-cyclopropyl-[1,8]-naphthyridine-3-carbonyl)-5-methyl-2,4dihydropyrazol-3-ones (6a-c), respectively. On the other hand, hydrazide (2) reacts with different aromatic aldehydes yields 2-cyclopropyl-[1,8]naphthyridine-3-carboxylic acid benzylidene-hydrazides (7a-g). Compounds (7a-g) on reaction with mercapto-acetic acid offered 3-[(2-cyclopropyl-[1,8]-naphthyridin-3-yl-methyl)amino]phenyl-thiazolidin-4-ones (8a-g). Interaction of acid hydrazide (2) with different aromatic acid chlorides afford N'-acetyl/benzoyl-2-cyclopropyl-1,8-naphthyridine-3-carbohydrazides (9a-d), which on treatment with POCl3 yield 2-cyclopropyl-[1,8]-naphthyridin-3-yl)-(5-phenyl-[1,3,4]-oxadiazol-2-yl)methanone (10a-d). -carboxylic acid ethyl ester.
Three 3-aryl-5-cyanopyrazolo[3,4-b]pyridines
Acta Crystallographica Section C Crystal Structure Communications, 1999
4-(4-Chlorophenyl)-5-cyano-3-(4-methylphenyl)-6-diphenyl-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine-dimethyl formamide (2/1), 2C 26 H 19 ClN 4 •C 3 H 7 NO, (I), 5-cyano-4-(4-methoxyphenyl)-3,6-diphenyl-4,7-dihydro-2H-pyrazolo[3,4-b]-pyridine, C 26 H 20 N 4 O, (II), and 3,4-bis(4-chlorophenyl)-5-cyano-6-phenyl-1H-pyrazolo[3,4-b]pyridine, C 25 H 14 Cl 2 N 4 , (III), were prepared from the corresponding 3-amino-5-arylpyrazoles and α-cyanochalcones. NMR solution studies (1H, 13 C, HSQC, HMBC, NOESY) of pyrazolo[3,4-b]pyridines, reveal the 2H-tautomers as being preferred in solution (DMSO-d 6). X-ray diffraction studies showed that (I) and (II) also have the 2H-tautomeric structures in the crystal structures. (III) is the aromatic crystalline product formed by oxidation of a 2H precusor during re-crystallization. (I) exists as hydrogen-bonded trimers (two pyrazolo[3,4-b]pyridine systems and a dimethyl formamide), (II) forms two-dimensional sheets and (III) is a centrosymmetric dimer. A paper discussing the chemistry of the above compounds is being prepared Experimental 4-(4-Chlorophenyl)-5-cyano-3-(4-methylphenyl)-6-diphenyl-4,7-dihydro-2H-pyrazolo[3,4b]pyridine-dimethylformamide (2/1), (I): a solution of 1.40 mmol of 3-amine-5-(4-methylphenyl)-1H-pyrazole and 1.40 mmol of 2-benzoyl-3-(4-chlorophenyl)-2-propenenitrile was heated in 50 ml of absolute ethanol for 1-2 h. After cooling, the reaction mixture was allowed to stand overnight. The resulting precipitate was filtered off, washed with cold ethanol and recrystallized from dimethyl formamide. 5-Cyano-4-(4-methoxyphenyl)-3,6-diphenyl-4,7-dihydro-2H-pyrazolo [3,4-b]pyridine, (II): a solution of 1.40 mmol of 3-amine-5-phenyl-1H-pyrazole and 1.40 mmol of 2-benzoyl-3-(4-methoxyphenyl)-2-propenenitrile was heated in 50 ml of absolute ethanol for 1-2 h. After cooling, the reaction mixture was allowed to stand overnight. The resulting precipitate was filtered off, washed with cold ethanol and recrystallized from ethanol. 3,4-Bis(4-chlorophenyl)-5-cyano-6-phenyl-1H-pyrazolo-[3,4-b]pyridine, (III): a solution of 1.40 mmol of 3-amine-5-(4chlorophenyl)-1H-pyrazole and 1.40 mmol of 2-benzoyl-3-(4-chlorophenyl)-2-propenenitrile was heated in 50 ml of absolute ethanol for 1-2 h. After cooling, the reaction mixture was allowed to stand overnight. The resulting precipitate was filtered off, washed with cold ethanol and recrystallized from ethanol. Refinement Compound (I) crystallized in the triclinic system; space group P1 assumed and confirmed by structure analysis. There are two independent molecules of the 2H-pyrazolo[3,4-b]pyridine derivative and one of the crystallization solvent (dimethyl formamide) in the asymmetric unit. Molecule (II) crystallized in the monoclinic system; space group C2/c or Cc from systematic absences; C2/c chosen and confirmed by the analysis. Molecule (III) crystallized in the monoclinic system; space group P2 1 /n from systematic absences. In all structures, H atoms were treated as riding atoms with C-H 0.95-1.00 Å, Data collection KappaCCD diffractometer 10310 independent reflections Absorption correction: Multi-scan (SORTAV; Blessing, 1995, 1997) 4898 reflections with I > 2σ(I) T min = 0.963, T max = 0.971 R int = 0.112