Synthesis of heierocyclic compounds from 2-phenyl-1, 2,3-triazole-4-formylhydrazine

2-Phenyl-1, 2, 3-triazole-4-formylhydrazine (2) was prepared by hydrazinolysis of the corresponding ester 1. Reaction of 2 with CS2/KOH gave the oxadiazole derivatives (3) which via, Mannich reaction with different dialkyl amines furnished 3-N, N-dialkyl derivatives (4a-c). Also, condensation of 2 with appropriate aromatic acid in POCl3 yielded oxadiazole derivatives (5a-c), or with aldehydes and ketones afforded hydrazones (6a-c). Cyclization of (6a-c) with acetic anhydride gave the desired dihydroxadiazole derivatives (7a-c). On the other hand, reaction of dithiocarbazate (8) with hydrazine hydrate gave the corresponding triazole derivative (9) which on treatment with carboxylic acids in refluxing POCl3 yielded s-triazole[3,4-b]-1, 3, 4-thiadiazole derivatives (10a-b). The structures of all the above compounds were confirmed by means of IR, 1H NMR, MS and elemental analysis.     

Synthesis and anticancer activity of some novel tetralin-6-yl-pyrazoline, 2-thioxopyrimidine, 2-oxopyridine, 2-thioxo-pyridine and 2-iminopyridine derivatives

The title compounds were prepared by reaction of 6-acetyltetralin (1) with different aromatic aldehydes 2a-c, namely 2,6-dichlorobenzaldehyde, 2,6-diflouro-benzaldehyde, and 3-ethoxy-4-hydroxybenzaldehyde, to yield the corresponding a,b-unsaturated ketones 3a-c. Compound 3b was reacted with hydrazine hydrate to yield the corresponding 2-pyrazoline 4, while compounds 3a,b reacted with thiourea to afford the 2-thioxopyrimidine derivatives 5a,b, respectively. The reaction of 1, and the aromatic aldehydes 2a-c with ethyl cyanoacetate, 2-cyano-thioacetamide or malononitrile in the presence of ammonium acetate yielded the corresponding 2-oxopyridines 6a,b, 2-thioxopyridines 7a-c or 2-iminopyridines 8a,b, respectively. The newly prepared compounds were evaluated for anticancer activity against two human tumor cell lines. Compound 3a showed the highest potency with IC(50) = 3.5 and 4.5 μg/mL against a cervix carcinoma cell line (Hela) and breast carcinoma cell line (MCF7), respectively.     

Synthesis of new v-triazolopyrimidinium salts

New v-triazolo[1,5-α]- and v-triazolo[1,5-c]pyrimidinium salts 12a-e, 13a-c have been synthesized via oxidation (i.e. cyclodehydrogenation) of the appropriate pyrimidyl ketone arylhydrazones 3a-e, 6a-c using TBB (2,4,4,6-tetrabromocyclohexa-2,5-dien-1-one) as the reagent. The arylhydrazones were obtained by standard reactions; the Grignard reaction of 2-cyano- and 4-cyanopyrimidine 1a,b, 4a-c gave 2-pyrimidyl- and 4-pyrimidyl ketones 2a-e, 5a-c , which reacted with arylhydrazines to yield the desired ketone arylhydrazones 3a-e, 6a-c.     

Preparation of polymer-supported Ru-TsDPEN catalysts and use for enantioselective synthesis of (S)-fluoxetine

Polymer-supported chiral ligands 9 and 17 were prepared based on Noyori's (1S,2S)- or (1R,2R)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine. The combination with [RuCl2(p-cymene)]2 has been shown to exhibit high activities and enantioselectivities for heterogeneous asymmetric transfer hydrogenation of aromatic ketones (19a-c) with formic acid-triethylamine azeotrope as the hydrogen donor, whereby affording the respective optically active alcohols 20a-c, the key precursors of chiral fluoxetine. As exemplified by ligand 17 for substrate 19c, the catalysts can be recovered and reused in three consecutive runs with no significant decline in enantioselectivity. The procedure avoids the plausible contamination of fluoxetine by the toxic transition metal species.     

Asymmetric Synthesis of 3-Hydroxyprolines by Photocyclization of N-(2-Benzoylethyl)glycinamides

The chiral N-(2-benzoylethyl)-N-tosylglycinamides 1a-c were prepared from the C₂-symmetric pyrrolidines 5a-c . Irradiation of these ketones 1a-c gave cis-3-hydroxyprolinamides 10-12 in moderate to good yields (Scheme 3). The de of the photocyclizations depended on the size of the substituents in positions C(2) and C(5) of the chiral pyrrolidine auxiliaries. In addition, the de varied with the reaction temperature, allowing the determination of activation-parameter differences. The structure of products 10-12 were established by NMR and X-ray analyses.     

Reactivity of p-phenyl substituted β-enamino compounds using K-10/ultrasound. I. Synthesis of pyrazoles and pyrazolinones

The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl-substituted)-2-buten-1-ones 1a-d and β-enamino esters, ethyl 3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d was systematically studied when allowed to react with hydrazine and methylhydrazine under solid support K -10/ultrasound conditions and in homogeneous media (reflux in ethanol or dichloromethane). The products were pyrazoles 2a-d , N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c . The regiochemistry of the cyclization reactions showed dependence upon the reaction conditions employed as well as upon the sub-stituent in the aromatic ring.     

Reactions of β-sulfenyl α,β-unsaturated ketones with guanidine,Amidines, and diamines

β-Sulfenyl α, β-unsaturated ketones 1a-c reacted with guanidine or amidines to give pyrimidine derivatives 3 in 14-76% yields. Treatment of ketones 1 with diamines such as ethylenediamine and o -phenylenediamine afforded the seven-membered heterocycles, 2,3-dihydro-1,4-diazepine 5 and 2,3-benzo-1,4-diazepines 8a-c .     

Reactivity of p-phenyl substituted β-Enamino compounds using K-10/ultrasound. II. Synthesis of isoxazoles and 5-Isoxazolones

The condensation of 4-phenyl substituted β-enamino ketones 1a-d and β-enamino esters 5a-d with hydroxylamine hydrochloride using K-10 as the solid support under sonication was studied to evaluate the formation of isoxazole and 5-isoxazolone rings from β-enamino compounds with a substituted aromatic ring. Isoxazoles 2a-c, 3c-d and 5-isoxazolones 6a-c and 7a-d were obtained. The use of K-10/ultrasound in this reaction furnished novel results in some cases.     

Synthesis, structure and catalytic properties of CNN pincer palladium(II) and ruthenium(II) complexes with N-substituted-2-aminomethyl-6-phenylpyridines

N-substituted-2-aminomethyl-6-phenylpyridines 2a-c have been easily prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a-c with PdCl(2) in toluene in the presence of triethylamine gave the CNN pincer Pd(II) complexes 3a-c in 18-28% yields. The CNN pincer Ru(II) complex 5 containing a Ru-NHR functionality could be obtained in a 71% yield by treatment of 2c with a Ru(II) precursor instead of PdCl(2). Additionally, the related CNN pincer Ru(II) complex 7 containing a Ru-NH(2) functionality has been synthesized by the reaction of 2-aminomethyl-6-phenylpyridine with the same Ru(II) precursor in a 68% yield. All the new compounds were characterized by elemental analysis (MS for ligands), (1)H, (13)C NMR, (31)P{(1)H} NMR (for Ru complexes) and IR spectra. Molecular structures of Pd complex 3c as well as Ru complexes 5 and 7 have been determined by X-ray single-crystal diffraction. The obtained Pd complexes 3a-c were effective catalysts for the allylation of aldehydes as well as for three-component allylation of aldehydes, arylamines and allyltributyltin and their activity was found to be much higher than a related NCN Pd(II) pincer in the allylation of aldehyde. On the other hand, the two new CNN pincer Ru(II) complexes 5 and 7 displayed excellent catalytic activity in the transfer hydrogenation of ketones in refluxing 2-propanol with the latter being much more active. The final TOF values were up to 4510 h(-1) with 0.01 mol% of 5 and 220,800 h(-1) with 0.005 mol% of 7, respectively.     

Synthesis and reduction of thieno[2′,3′(3′,2′ or 3′,4′):5,6]-azocino[2,1-a]isoindole-7, 13-diones

A synthesis of the thieno[2′,3′(3′,2′ or 3′,4′):5,6]azocino[2,1-a]isoindole-7,13-diones 6a-c was developed from N-thienylethylphthalimides 3a-c using a Wittig reaction followed by a Friedel-Crafts cyclization of acetic acid derivatives 5a-c . Reduction of ketones 6a-c into alcohols 7a-c was stereo specific.     

Novel phosphine-catalyzed zipper cyclization of aliphatic diyne-dione and yne-dione systems

[reaction: see text] An unexpected tri-n-butylphosphine-catalyzed zipper cyclization of diyne[bond]diones (1a-d) or yne-diones (1e and 1f) is described. Bicyclic ketones (2a, 2b, 2c, 2e, and 2f) with five- or six-membered rings fused to the five-membered ring were obtained from both aliphatic diyne-diones (1a-c) and yne-diones (1e and 1f) having tetra- or pentamethylene spacers. The bicyclic products (2) were produced with high diastereoselectivity.     

Synthetic organic chemistry with 2-ethoxy-2-(phenylselenenyl)perfluoroalk-2-enenitrile: application to alpha-cyanoperfluoroacylation of aldehydes

(Z)- and (E)-2-Ethoxyperfluoro-2-(phenylselenenyl)alk-2-enenitriles 2-4 prepared by our original method underwent transmetalation on treatment with n-BuLi or EtMgBr, and the successive reaction with aldehyde and ketones afforded the corresponding allylic alcohols 10a-f, 9a, and 11a,b in good to high yields. Hydrolysis of the alcohols gave alpha-cyano-alpha,beta-unsaturated perfluoroalkyl ketones 13a-c, 13e, 12a, and 15a. alpha-Cyanoperfluoroalkyl ketones were easily converted to alpha,beta-unsaturated 3-aryl-2-cyanoallylic alcohols 18-22 having interesting biological activities and chemical reactivities.     

Reactions of β-Sulfinyl α,β-Unsaturated Ketones with Dienes

β-Sulfinyl α,β-unsaturated ketones (2a-f) reacted in a regioselective manner with dienes such as butadiene (3a) and 1,3-pentadiene (3b) to give 1,4-cyclohexadiene derivatives (4-8) with the concomitant elimination of sulfenic acid, while the ketones (2a-c) reacted with cyclopentadiene (3c) to yield the norbornenes (9).     

Nadh models-19Cyclopropane ring as a chemical probe in the study of the mechanism of hydrogen transfer by 1,4-dihydropyridine derivatives

N-(Cyclopropylmethylene)phenylamines (1a-c), cyclopropyl 2-pyridyl ketones (5-c) and ethyl cyclopropylmethlenepyruvate (14) have been subjected to reduction by l,4-dihydropyridines [3,5-diethoxycarbonyl-2,6-dimethyl-l,4-dihydropyridine (2) and/or 1-benzyl-1,4-dihydronicotinamide (7)]in the presence of magnesium ions, and by tin hydrides. The reactions with 1,4-dihydropyridines do not involve cleavage of the three-membered ring in the reduction step. The observed acyclic product from 2-pyridyl 2,2-dimethylcyclopropyl ketone (5b) is a consequence of ring cleavage prior to reduction of the carbonyl function. In contrast, reduction of 1a-c and 5-c by tin hydrides leads to products in which the cylopropane moiety has undergone ring-opening. These findings support a hydride transfer mechanism for reductions with NADH models.     

Reactions of O-methyl o-quinone monoximes with methyl-, methylene- and methine- substituted aromatic compounds. Synthesis of benzo[d]oxazole and 1,4-benzoxazine derivatives

O-Methyl o-quinone monoxime 1 reacts thermally with compounds 2a-d or 6a,b or 7a,b to give mainly the corresponding 2-substituted phenanthroxazoles 3a-c and 8 . The reaction of 1 with aromatic methylene compounds lOa-c affords the ketones 13a-c in moderate to high yields. Similar products are also obtained from the reaction of monoximes 15a,b with some of the above reactants. The unexpected products 5 and 20 are obtained from the reaction of 1 with 2-methylimidazole ( 2d ) and with phenyloxirane ( 19 ) respectively, while the 4H-1,4-oxazine derivative 23 is obtained from the reaction of 1 with indene ( 21 ).     

Reactivity of p-phenyl substituted β-enamino compounds using k-10/ultrasound. I. synthesis of pyrazoles and pyrazolinones

The reactivity of the β-enamino ketones, 3-amino-1-(p-phenyl-substituted)-2-buten-1-ones 1a-d and β-enamino esters. Ethyl-3-amino-3-(p-phenyl-substituted)-2-propenoates 5a-d were evaluated by systematic studies of the reactions with hydrazine and methylhydrazine by reactions with solid support K-10/ultrasound and homogeneous media (reflux in ethanol or dichloromethane) yielding pyrazole rings 2a-d , N-methylpyrazoles 3a-d, 4a-d and N-methylpyrazolinones 6a-c and 7a-c . The regiochemistry of the cyclization showed dependence of the reaction conditions employed as well as the substituent in the aromatic ring.     

Efficient synthesis of substituted vinyl ethers using the Julia olefination

Julia olefination between alpha-alkoxy sulfones 2a-c and a wide variety of ketones or aldehydes afforded substituted vinyl ethers in 46-90% yields. Sulfones 2a-c were readily prepared in two steps from commercially available reagents in 68-80% yields. Optimization revealed that the nature of the base, the solvent, and the temperature were crucial to obtaining the desired vinyl ethers. [reaction: see text]     

A general preparation of pyridines and pyridones via the annulation of ketones and esters

A general preparation of pyridines 4a-f from stabilized ketones 3a-c and aryl ketones 3d-f is described. The annulation of stabilized esters 3g,h gives access to the corresponding 2-pyridones 4g,h. The annulation reactions proceed in fair to excellent yields (46-87%) with vinamidinium hexafluorophosphate salts 2a-d containing electron-withdrawing groups at the beta-position. The mechanism of the reaction was investigated by NMR and proceeds through the formation of a dienaminone intermediate.     

A novel sequential aminodiene Diels-Alder strategy for the rapid construction of substituted analogues of Kornfeld's ketone

Through a novel sequence of aminodiene Diels-Alder reactions, amidofurans 18a-c were converted to tricyclic ketones 21a-c in moderate to good yields. Ketone 21a could be converted to Uhlé's ketone (6) by cleaving the tert-butyl carbamate and oxidatively removing the methyl ester. Tricycle 21a readily underwent bromination to give 22. Formation of the corresponding enol triflate 25 followed by carbonylation gave ester 27, which was then coupled with N-methyl propriolamide to furnish 26. [reaction: see text]     

The Behavior of 3,4,5-Trimethoxybenzylidenemalononitrile Towards Alkyl Phosphites

3,4,5-Trimethoxybenzylidenemalononitrile 1 reacts with trialkyl phosphites 2a-c in the absence of solvent to give the phosphonate derivatives 4a-c . The dimeric compound 6 also was produced in the reaction with 2c . The phosphonates 8a-c were produced when compound 1 was allowed to react with dialkyl phosphites 3a-c under the same experimental conditions. A mechanism is proposed to explain the formation of compounds 4 and 6 .