- Regio- and stereoselective synthesis of spiro-heterocycles bearing the pyrazole scaffold via [3+2] cycloaddition reaction
-
Herein we reported the utility of one-pot multicomponent based [3+2] cycloaddition reaction transformation to prepare a new two hybrids of spirooxindoles engrafted with pyrazole skeleton. Upon treatment of the electron-deficient olefins based pyrazole motif with in situ the generated azomethine ylides (AY) of sarcosine with the 6-chloro-isatin afforded spiroadducts. To enlighten the regio- and diastereo-selectivity of these spiroheterocycles, single crystal X-ray diffraction analysis was presented. Using Hirshfeld calculations, many short distance contacts such as O…H, Cl…H, N…H, H…C, C…C and Cl…S have a great impact on the molecular packing and the crystal stability of 8a and 8b. The latter showed some Cl…Cl inter halogen interactions (Cl1…Cl3; 3.358 ?). In addition, DFT calculations were used to compute the electronic properties as well as the 1H- and 13C-NMR spectra of the studied systems. Both compounds are polar where 8b (3.995 Debye) has higher dipole moment than 8a (3.414 Debye). The NMR chemical shifts were calculated and found in excellent correlations between the calculated and experimental data were obtained (R2 = 0.94–0.98).
- Islam, Mohammad Shahidul,Haukka, Matti,Soliman, Saied M.,Al-Majid, Abdullah Mohammed,Rahman, A.F.M. Motiur,Bari, Ahmed,Barakat, Assem
-
-
- Reactivity and Anticancer Assessment of 4-Hydroxyquinoline Derivatives
-
Abstract: Ethyl 4-hydroxy-7-(trifluoromethyl)quinoline-3-carboxylate (1) exhibits a moderate cytotoxic activity against the MCF-7 mammary gland cancer cell line and HePG2 hepatocellular carcinoma cell line and a weak activity against the HCT-116 human colorectal carcinoma cell line. In order to enhance the cytotoxic activity of this compound, it was modified by changing the side-chain substituent and/or forming a new heterocyclic ring fused to the pyridine ring. Heating compound 1 with chloroacetyl chloride gave a mixture of two isomeric O-acylation products ethyl 4-(2-chloroacetoxy)-7-(trifluoromethyl)-quinoline-3-carboxylate and 3-chloro-8-(trifluoromethyl)-2H-pyrano[3,2-c]quinoline-2,4(3H)-dione, whereas the reaction with acetyl chloride in NaOH formed an N-acylation product 1-acetyl-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid. The reactions of compound 1 with urea, thiourea, hydrazine hydrate, hydroxylamine, o-phenylenediamine, phenyl isothiocyanate, and ethyl acetoacetate yielded the corresponding condensation products 1-[4-oxo-7-(trifluoromethyl)-3,4-dihydroquinoline-3-carbonyl)]urea, 1-[4-oxo-7-(trifluoromethyl)-3,4-dihydroquinoline-3-carbonyl)]thiourea, 7-(trifluoromethyl)-1,2-dihydropyrazolo[4,3-c]quinolin-3-one, 7-(trifluoromethyl)isoxazolo[4,5-c]quinolin-3(2H)-one, 3-(trifluoromethyl)-13H-benzo[2,3][1,4]diazepino[6,5-c]quinolin-7-ol, 3-phenyl-2-thioxo-8-(trifluoromethyl)-2,3-dihydro-4H-[1,3]oxazino[5,6-c]quinolin-4-one and ethyl 8-(trifluoromethyl)-2-methyl-4-oxo-4H-pyrano[3,2-c]quinolone 3-carboxylate, respectively. The structures of the synthesized compounds were confirmed by elemental analysis and spectral data.
- El-Metwally, S. A.,Regal, M. K. A.,Shabana, S. S.
-
p. 307 - 314
(2020/04/17)
-
- 2-Bromo-1-(1H-pyrazol-4-yl)ethanone: Versatile Precursor for Novel Mono- and Bis[pyrazolylthiazoles]
-
The synthesis of novel bis(thiazoles) 20a, 20b, 20c and 23a, 23b, 23c is reported. Thus, reaction of 2-bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethanone (6) with the corresponding thioamide derivatives 7a,7b, in refluxing EtOH in the presence of triethylamine, afforded 4-pyrazolylthiazoles 8a, 8b in good yields. On the other hand, the novel bis(thiazoles) 20a, 20b, 20c and 23a, 23b, 23c were obtained from the reaction of 6 with the corresponding benzaldehyde thiosemicarbazones 19a, 19b, 19c, 22a, 22b, 22c in refluxing EtOH. Compounds 19a, 19b, 19c and 22a, 22b, 22c were obtained by condensation of the corresponding bis(aldehydes) 18a, 18b, 18c and 21a, 21b, 21c with thiosemicarbazide.
- Salem, Mostafa E.,Darweesh, Ahmed F.,Mekky, Ahmed E. M.,Farag, Ahmad M.,Elwahy, Ahmed H. M.
-
p. 226 - 234
(2017/02/03)
-
- N → N acyl group migration in N-acylpyrazoles: Isomerization of 1,4-diacyl-5-methyl-1H-pyrazoles to 1,4-diacyl-3-methyl-1H-pyrazoles
-
1,4-Diacyl-5-methyl-1H-pyrazoles on heating in toluene undergo isomerization to 1,4-diacyl-3-methyl-1H-pyrazoles via intermolecular N → N acyl group migration. 1,4,5-Trisubstituted pyrazoles obtained by reaction of 2-ethoxymethylidene derivatives of 1,3-diketones with 1,3-benzothiazol-2-ylhydrazine or phenylhydrazine failed to isomerize to 1,3,4-trisubstituted pyrazoles.
- Petrov,Pakal’nis,Zerov,Yakimovich
-
p. 381 - 392
(2017/05/10)
-
- 2-Bromo-1-(1H-pyrazol-4-yl)ethanone: Versatile precursors for novel mono-, bis- and poly{6-(1H-pyrazol-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines}
-
A simple synthesis of novel mono-, bis- and poly{6-(1H-pyrazol-4-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines} is reported. The formation of the target compounds was achieved by the reaction of 2-bromo-1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethanone with the appropriate aminotriazolethiol or by the reaction of 6-pyrazolyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-3-thiol with the appropriate di- and poly(bromo) compounds. The structures of the newly synthesized compounds were established by spectroscopy and elemental analyses.
- Salem, Mostafa E.,Darweesh, Ahmed F.,Farag, Ahmad M.,Elwahy, Ahmed H.M.
-
p. 712 - 719
(2016/01/15)
-
- Design and regioselective synthesis of trifluoromethylquinolone derivatives as potent antimicrobial agents
-
Three series of new trifluoromethyl substituted quinolone derivatives were synthesized (4a-f, 6a-f and 8a-f) from corresponding substituted anilines by multi-step reactions. The regioselective alkylation with different alkyl halides were carried out by approaching two different routes to get the final products in good yield. Newly synthesized compounds were characterized by spectral study and also by C, H, N analyses. Three dimensional structure of 2b and 4b were also confirmed by single crystal X-ray studies. The final compounds (4a-f, 6a-f and 8a-f) were screened for their in-vitro antibacterial and antifungal activity by well plate method (zone of inhibition). The results revealed that, compounds 4a, 6b, 6c and 8e showed significant antibacterial activity as compared to the standard drug Ciprofloxacin. The compound 8a was found to be a potent antifungal agent.
- Garudachari,Isloor, Arun M.,Satyanarayana,Fun, Hoong-Kun,Pavithra,Kulal, Ananda
-
p. 422 - 432
(2013/10/01)
-
- One-pot regioselective synthesis of 1,4,5-trisubstituted pyrazoles under solvent-free conditions without catalyst
-
A fast, one pot method with excellent yield has been developed for preparation of 1,4,5-trisubstituted pyrazoles. Treatment of β-dicarbonyl compounds with N,N-dimethylformamide dimethylacetal and hydrazine derivatives afforded immediately the desired pyrazoles under solvent-free conditions in the absence of catalyst. Springer-Verlag 2012.
- Alinezhad, Heshmatollah,Tajbakhsh, Mahmood,Zare, Mahboobeh
-
experimental part
p. 947 - 950
(2012/08/07)
-
- Catalyst-free one-pot synthesis of 1,4,5-trisubstituted pyrazoles in 2,2,2-trifluoroethanol
-
A simple, efficient and three component one-pot synthesis of 1,4,5-trisubstituted pyrazoles by condensation of β-dicarbonyls, N,N-dimethylformamide dimethyl acetal (DMFDMA) and hydrazine derivatives in 2,2,2-trifluoroethanol without using any catalyst and activation, is described.
- Alinezhad, Heshmatollah,Tajbakhsh, Mahmood,Zare, Mahboobeh
-
experimental part
p. 995 - 1000
(2011/11/06)
-
- Synthesis of 1-aryl-5-methyl-4-[4-aryl-6-(3-oxo-1,4-benzothiazin-6-yl) pyrid-2-yl]pyrazoles and 1-aryl-5-methyl-4-[2-amino-4-aryl-pyrimidin-6-yl] pyrazoles as antibacterial agents
-
A series of 1-Aryl-5-methyl-4-[4-aryl-6-3-oxo-1,4-benzothiazin-6-yl)pyrid- 2-yl]pyrazoles (6a-g) and 1-Aryl-5-methyl-4-[2-amino-4-arylpyrimidin-6-yl] pyrazoles (7a-d) have been synthesized and tested for their antibacterial activity.
- Ashok,Pallavi,Jagath Reddy,Srinivasa Rao
-
-
- Aqueous one-pot synthesis of pyrazoles, pyrimidines and isoxazoles promoted by microwave irradiation
-
Microwave irradiation promotes the conversion of enaminoketones formed in situ into a variety of heterocycles by reaction with the appropriate bidentate nucleophile. The advantages of the method over previous approaches are short reaction times and facile purification by precipitation of the products in aqueous media. Moreover the convenient one-pot procedure makes these syntheses particularly suitable for library production. Organic reactions in aqueous media have become of great interest as water is not only more environmentally friendly, but also because organic reactions in water often display unique reactivity and selectivity.
- Molteni, Valentina,Hamilton, Matthew M.,Mao, Long,Crane, Christine M.,Termin, Andreas P.,Wilson, Dean M.
-
p. 1669 - 1674
(2007/10/03)
-
- Oxazolo, thiazolo and selenazolo [4,5-c]-quinolin-4-amines and analogs thereof
-
Thiazolo-, oxazolo- and selenazolo[4,5-c]quinolin-4-amines and analogs thereof are described including methods of manufacture and the use of novel intermediates. The compounds are immunomodulators and induce cytokine biosynthesis, including interferon and/or tumor biosynthesis, necrosis factor, and inhibit the T-helper-type 2 immune response. The compounds are further useful in the treatment of viral and neoplastic diseases.
- -
-
-
- Structure-activity relationships for antiplasmodial activity among 7- substituted 4-aminoquinolines
-
Aminoquinolines (AQs) with diaminoalkane side chains (-HNRNEt2) shorter or longer than the isopentyl side chain [-HNCHMe(CH2)3NEt2] of chloroquine are active against both chloroquine-susceptible and -resistant Plasmodium falciparum. (De, D.; et al. Am. J. Trop. Med. Hyg. 1996, 55, 579-583). In the studies reported here, we examined structure-activity relationships (SARs) among AQs with different N,N-diethyldiaminoalkane side chains and different substituents at the 7-position occupied by Cl in chloroquine. 7-Iodo- and 7- bromo-AQs with diaminoalkane side chains [-HN(CH2)2NEt2, -HN(CH2)3NEt2, or -HNCHMeCH2NEt2] were as active as the corresponding 7-chloro-AQs against both chloroquine-susceptible and -resistant P. falciparum (IC50s of 3-12 nM). In contrast, with one exception, 7-fluoro-AQs and 7-trifluoromethyl-AQs were less active against chloroquine-susceptible P. falciparum (IC50s of 15-50 nM) and substantially less active against chloroquine-resistant P. falciparum (IC50s of 18-500 nM). Furthermore, most 7-OMe-AQs were inactive against both chloroquine-susceptible (IC50s of 17-150 nM) and -resistant P. falciparum (IC50s of 90-3000 nM).
- De, Dibyendu,Krogstad, Frances M.,Byers, Larry D.,Krogstad, Donald J.
-
p. 4918 - 4926
(2007/10/03)
-
- Study of the reaction of 2-acyl 1,3-dicarbonyl compounds with hydrazines by 1H NMR spectroscopy
-
The reaction of 2-acyl 1,3-dicarbonyl compounds with hydrazine and phenylhydrazine was studied by 1H NMR spectroscopy.It was shown that the formation of functionally 4-substituted pyrazoles is promoted if the reaction is conducted in protic solvents at reduced temperature.The presence of the benzoyl groups in the 2-acyl 1,3-dicarbonyl compounds leads to the preferential formation of the cleavage products, i.e., the corresponding acylhydrazines and 1,3-dicarbonyl compounds.It was established that the initial reaction product is consumed in two directions, i.e., cyclization with the formation of functionally 4-substituted pyyrazoles and cleavage with the formation of acetylhydrazines and the corresponding 1,3-dicarbonyl compounds.
- Emelina, E. E.,Ershov, B. A.,Zelenin, A. K.,Selivanov, S. I.
-
p. 1630 - 1636
(2007/10/03)
-
- Synthese regiospecifique d'acyl-4 pyrazoles a partir d'acyl-5 pyrimidines
-
The transformation of variously substituted 5-acetyl-4-methylpyrimidines 1 into 4-acetyl-1-amidino-3-methylpyrazole amidinohydrazone dihydrochloride 3, under the action of amidinohydrazine hydrochloride, in boiling acidic methanolic solution, depends on the nature of the 2-substituent of pyrimidines 1, and on the stability of the amidinohydrazone of pyrimidines 2 under the reaction conditions.Phenylhydrazine transforms all the pyrimidines 1 into pyrazoles, regiospecifically or not, according to the nature of the 2-substituent of pyrimidines 1.This new possibility of ring contraction has been extended to other unsymetrical 5-acyl- and 5-ethoxycarbonylpyrimidines.
- Bajnati, Abdelilah,Kokel, Bruno,Hubert-Habart, Michel
-
p. 318 - 324
(2007/10/02)
-
- Reaction of 2-Dimethylaminomethylene-1,3-diones with Dinucleophiles. I. Synthesis of 1,5-Disubstituted 4-Acylpyrazoles
-
Reaction of open-chain and cyclic sym-1,3-diones with N,N-dimethylformamide dimethyl acetal gave, generally in high yield, a series of sym-2-dimethylaminomethylene-1,3-diones which reacted with phenylhydrazine and methylhydrazine to afford, generally in satisfactory yield, a number of 1,5-disubstituted 4-acylpyrazoles.The applications and limits of this new pyrazole synthesis are presented and discussed.
- Schenone, Pietro,Mosti, Luisa,Menozzi, Giulia
-
p. 1355 - 1361
(2007/10/02)
-
