Halo Esters Research Articles

Synthesis, Characterization, and Anticancer Screening of Some New Bithiazole Derivatives

Twenty new bithiazole derivatives were synthesized by condensation of 2-{2-[(1-arylethylidene)hydrazinylidene]thiazolidin-4-ylidene}hydrazine-1-carbothioamides with halo ketones, halo esters, and α-keto hydrazonoyl halides. The structures of all prepared compounds were proposed on the basis of their IR,1H and 13C NMR, and mass spectra. All the synthesized compounds were screened for their cytotoxicity against three human cancer cell lines, HCT-116 (human colorectal carcinoma), MCF-7 (human breast adenocarcinoma), and HepG2 (human hepatocellular carcinoma). Two compounds (12d and 12b) had significantly more potent anticancer activity on HCT-116 human colorectal carcinoma cells. In the case of MCF-7 human breast cancer cells, three compounds (12b, 4b and 4a) were significantly more potent than the reference drug doxorubicin. Nine of the synthesized compounds (8a, 7a, 9b, 12d, 12c, 7b, 10a, 5a and 12b) showed a significantly higher activity than that of doxorubicin against HepG2 human liver cancer cells.

Synthesis of some new thiazole derivatives and their cytotoxicity on different human tumor cell lines

Some novel 1-(inden-3-ylidene)-2-(thiazol-2-ylidene)hydrazine derivatives 3–9 were synthesized by the Hantzsch reaction of thiosemicarbazone derivatives 2a–2c with halo ketones and halo esters. Thiosemicarbazone derivatives reacted with hydrozonyl chlorides to give diazenyl-4-methylthiazole derivatives 11a–11d. Structures of the products were elucidated from IR, 1H, and 13C NMR, and Mass spectra elucidate. The synthesized compounds were screened for their cytotoxicity against three human tumor cell lines. Twenty compounds showed high (≥60 %) antiproliferative activity over breast cancer (MCF-7). Compounds 2b, 3c, 4a, 4b, 6b, 6c, 7b, 8a, and 11b possessed higher cytotoxic activity over breast tumor cell line than Doxorubicin.

Some Chemical Aspects of 1,2,4-triazine derivatives

Condensation of 3a,b with some aromatic aldehydes afforded the Schiff bases (4a-f). Reaction of 3a,b witharomatic aldehydes and alkyl phosphites gave the corresponding amino phosphonates (5a-d). Heating 3a,b with 6a-f in POCl3 at85 °C furnished the amino sulphonamides (7a- l). Acid hydrolysis of compounds 7a,b and 7k) furnished the amines (8a-c).Condensation of 3a, b with 9a,b afforded the cyclized product (10a,b). Reaction of 3a with halo esters afforded 12 and 13.Heating 3a,b with 14a-c afforded 15a-f. Hydrolysis of 15a,b afforded 16a,b. Fusion of 3a,b with 1,4-butane sultone gave sultams(18a,b). The antimicrobial activity o9f some products was tried

Dynamic Kinetic Resolution of L-Threonine-derived α-Bromo Esters for Asymmetric Synthesis of α-Amino Esters

Many chiral alcohols have successfully been used as a chiral auxiliary for the dynamic resolution of -halo esters in nucleophilic substitution. 1 L-Threonine is a proteinogenic -amino acid that bears a chiral alcohol group. However, so far L-threonine has not been used as a chiral auxiliary for the dynamic resolution of -halo esters. We herein report the first example of L-threonine-mediated dynamic kinetic resolution of -bromo esters in nucleophilic substitution with various amine nucleophiles. Treatment of N-acetyl L-threonine isopropyl ester with racemic -bromo phenylacetic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) provided -bromo ester (RS)-1 in 70% yield with about 50:50 diastereomeric ratio (dr). When the mixture of (S)-1 and (R)-1 was treated with p-anisidine (1.2 equiv), tetrabutylammonium iodide (TBAI, 1.0 equiv) and diisopropylethylamine (DIEA, 1.0 equiv) in CH2Cl2 at room temperature for 12 h, amino ester 8a was produced in 63% yield with 84:16 dr as shown in Table 1, entry 1. Also, six different N-protection groups of L-threonine were examined for the substitution with p-anisidine as shown in entries 2-7. The reactions of 2, 3, 4, and 7 bearing N-pivaloyl, N-Boc, Nbenzoyl, and N,N-dibenzyl groups gave slightly better drs ranging from 88:12 to 86:14, while the reactions of 5 and 6 bearing N-p-methoxybenzoyl and N-2-pyridinylcarbonyl groups gave lower drs compared to the reaction of 1. The dr and yield of the substitutions in Table 1 imply that -bromo carbon center is configurationally labile with respect to the rate of substitution and L-threonine-derived -bromo esters

Synthesis, characterization and biological evaluation of thiazolopyrimidine derivatives

Different substituted diesters of thiazolopyrimidine were prepared by the treatment of 3,4 dihydropyrimidine2-thione with α-haloesters using ethanol under reflux condition affording 71–85% yield. IR, 1HNMR, 13CNMR and elemental analyses were used for the characterization of these compounds. The crystal and molecular structure of one of the product, 5-phenyl-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidine-2,6-dicarboxylic acid diethyl ester (3e) was verified by single crystal X-ray diffraction method. The antimicrobial activity was evaluated against four bacterial strains and one fungal species. Few of the derivatives exhibited antibacterial and antifungal activities. We have reported the synthesis of some thiazolopyrimidine derivatives by cyclo-condensation of dihydropyrimidine with halo esters. Crystal structure analysis of one of the derivatives has been carried out. Some of the derivatives exhibited antibacterial and antifungal activities.

Synthesis, molecular docking study and antitumor activity of novel 2-phenylindole derivatives

The starting material, 4-(1-indol-2-yl)phenol 1 was obtained via Fischer synthesis. Vilsmeir Haack ’s formylation of 1 gave the carboxaldehyde derivative 2 which was subjected to different reactions affording the 3-substituted compounds 3– 10. Compound 1 reacted with halo esters to give 11 and 12a, b. The reaction of 12a with various amino derivatives gave compounds 13– 16. The hydrazide derivative 15a reacted with 1,3-diketones, ethyl acetoacetate and aromatic carboxylic acid derivatives to give 17a, b, 18 and 19a– e, respectively. Antitumor activity of target compounds were tested against breast cancer cell lines (MCF-7) and (MDA-MB-231). The most potent compound was 3e with IC 50 = 1.60 nM against (MCF-7). Docking was performed on colchicine binding site of tubulin to study the binding mode of the designed compounds.

Indium(III) bromide catalyzed cleavage of cyclic and acyclic ethers: An efficient and practical ring opening reaction

Ethers undergo smooth cleavage with acyl chloride in the presence of catalytic amount of indium(III) bromide under mild conditions to give the corresponding halo esters. This new procedure offers significant advantages, such as high conversions, short reaction times and enhanced selectivity together with mild reaction conditions.

Synthesis and structural characterization of 1- and 2-substituted indazoles: ester and carboxylic acid derivatives.

A series of indazoles substituted at the N-1 and N-2 positions with ester-containing side chains -(CH2)(n)CO2R of different lengths (n = 0-6, 9, 10) are described. Nucleophilic substitution reactions on halo esters (X(CH2)(n)CO2R) by 1H-indazole inalkaline solution lead to mixtures of N-1 and N-2 isomers, in which the N-1 isomer predominates. Basic hydrolysis of the ester derivatives allowed the synthesis of the corresponding indazole carboxylic acids. All compounds were fully characterised by multinuclear NMR and IR spectroscopies, MS spectrometry and elemental analysis; the NMR spectroscopic data were used for structural assignment of the N-1 and N-2 isomers. The molecular structure of indazol-2-yl-acetic acid (5b) was determined by X-ray diffraction, which shows a supramolecular architecture involving O2-H...N1 intermolecular hydrogen bonds.

Mild and efficient method for the cleavage of cyclic and acyclic ethers by iodine under solvent-free conditions

Ethers undergo smooth cleavage with acyl chlorides in the presence of a catalytic amount of elemental iodine under extremely mild conditions to give the corresponding halo esters. This new procedure offers significant advantages such as high conversions, short reaction times and enhanced selectivity together with mild reaction conditions, which makes it an attractive strategy.

A novel esterase from Bacillus subtilis (RRL 1789): Purification and characterization of the enzyme

An esterase (EC 3.1.1.1) produced by an isolated strain of Bacillus subtilis RRL 1789 exhibited moderate to high enantioselectivity in the kinetic resolution of several substrates like aryl carbinols, hydroxy esters, and halo esters. The enzyme named as B. subtilis esterase (BSE), was purified to >95% purity with a specific activity of 944 U/mg protein and 12% overall yield. The purified enzyme is ∼52 kDa monomer, maximally activity at 37 °C and pH 8.0 and fairly stable up to 55 °C. The enzyme does not exhibit the phenomenon of interfacial activation with tributyrin and p-nitrophenyl butyrate beyond the saturation concentration. The enzyme showed preference for triacyglycerols and esters of p-nitrophenol with short chain fatty acid. Presence of Ca 2+ ions increases the activity of enzyme by ∼20% but its presence does not have any influence on the thermostability of the enzyme. The enzyme is not a metalloprotein and belongs to the family of serine proteases. The N-terminal amino acid sequence of BSE determined, as Met-Thr-Pro-Glu-Iso-Val-Thr-Thr-Glu-Tyr-Gly- revealed similarity with the N-terminal amino acid sequence of p-nitrobenzylesterase of B. subtilis.

New heterocycles from thienopyridocinnolines

3-Cyano-4-(p-tolyl)pyrido[3,2-c]cinnolin-2(1H) thione 3 was reacted with α -halo ketones, esters, or amides to give the intermediates, S-alkylated products 5b-h, respectively, which underwent intramolecular ring closure reactions with ethanolic sodium ethoxide to give thienopyridocinnolines 6a-h. Pyrimidothienopyridocinnolines 9 and 11 were obtained by treatment of oxazino compound 8 with hydrazine hydrate and ammonium acetate. Treatment of hydrazino derivative 13 with acetylacetone, triethylorthoformate, carbon disulphide, ethyl chloroformate, and acetic anhydride afforded triazolopyrimidothienopyridocinnolines 14-16, 18, and 21, while with nitrous acid the corresponding tetrazolo compound 19 was produced.Key words: thienopyridocinnolines; their pyrimido, triazolopyrimido, and heteroannelated systems.

Alkylation-annulation of halo esters with organometallic reagent/SmI 2 couple leading to cycloalkanols: A facile cyclopropanol synthesis from a 3-halo ester

Transformation of a 3-halo ester to cyclopropanols has been accomplished in excellent yields under mild conditions employing a coupled reagent of samarium(II) diiodide with organometallic reagents. 5- and 6- Halo esters were also transformed into cyclopentanols and cyclohexanols, respectively, in low to moderate yields. The reaction with a 4-halo ester gave 2,2-disubstituted tetrahydrofuran as a major product that resulted from double alkylation followed by cyclization; a substituted cyclobutanol was formed in poor yield.

Synthesis of Some New Thieno[2,3-b][1,6]naphthyridines and Related Compounds

Abstract 3,5-Dibenzylidene-1-isopropy1-4-piperidinone (1) reacts with cyanothioacetamide to give 1,6-naphthyridine-2(1H) thione derivative 2. Reaction of 2 with halo ketones or halo esters followed by ring closure gives thieno[2,3-b][1,6]naphthyridine derivatives 5a—i, which are used as versatile intermediates in the synthesis of related heterocyclic ring systems as pyrimidothienonaphthyridines 10, 11, 14, and 15, oxazinothienonaphthyridine (13) and triazinothienonaphthyridine (9).

A novel one-pot synthesis of functionalized perfluoroalkylated 1,4-alkadienes

A novel one-pot synthesis of functionalized perfluoroalkylated 1,4-alkadienes via the Reformatsky reaction of unsaturated halo esters with fluorinated β-ketophosphonium salts is described. This new methodology provides a four-carbon homologation giving functionalized perfluoroalkylated 1,4-alkadienes exclusively in 37–55% yields (three steps).

ChemInform Abstract: The Chemoselective Reduction of Fluorinated Halo Esters with Sodium Borohydride. Fluorinated Haloalkanols and Their (Meth)Acrylates.

AbstractThe synthesis and reaction of several fluorinated halo esters (IV) are described.

Activation of hydrogen by cationic cyclopentadienyl complexes with sulfido ligands. 3. Cationic complexes derived from reactions with halo esters, halo ketones, and acyl halides

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTActivation of hydrogen by cationic cyclopentadienyl complexes with sulfido ligands. 3. Cationic complexes derived from reactions with halo esters, halo ketones, and acyl halidesD. E. Coons, R. C. Haltiwanger, and M. Rakowski. DuBoisCite this: Organometallics 1987, 6, 11, 2417–2425Publication Date (Print):November 1, 1987Publication History Published online1 May 2002Published inissue 1 November 1987https://doi.org/10.1021/om00154a024RIGHTS & PERMISSIONSArticle Views62Altmetric-Citations17LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Fatty acids: part 27. Olefin inversion involving unsaturated fatty esters

AbstractUnsaturated long chain fatty esters gave the corresponding bromochloro ester derivatives when treated with N‐bromosuccinimide and hydrogen chloride. Treatment of the intermediate halo esters with sodium iodide furnished the same positional unsaturated fatty ester isomers, but of opposite geometric configuration. This olefin isomerization method was found to be high yielding, stereospecific and to cause no double bond migration.

Structure-gas chromatographic electron capture sensitivity relationships of some substituted 17α-acetoxyprogesterones

Structure-electron capture sensitivity relationships were established for underivatized 17α-acetoxyprogesterones. While progesterone was very insensitive, 17α-acetoxyprogesterone had a response of 4.8 × 10 2 C/mole. Methyl groups in the A or B ring of 17α-acetoxyprogesterone had no effect. A keto group at C-6 was 25 times more sensitive (1.2 × 10 4 C/mole). A double bond at C-6,7 enhanced the sensitivity sevenfold (3.5 × 10 3 C/mole), but double bonds at C-1,2 or C-9,11 had only slight effect. Substitution at C-16 was important. A methyl group at C-16 had two and three times the sensitivity in the 3-keto Δ 4 and 3-keto Δ 4,6 series (1.1 × 10 3 and 1.1 × 10 4 C/mole), respectively. A methylene group at C-16, in contrast, showed a six- and twofold greater sensitivity over the C-16 methyl in the two series (7 × 10 3 and 2.2 × 10 4 C/mole), respectively. The most sensitive compound was 6-dehydro-6-methyl-16-methylene-17α-acetoxyprogesterone (melengestrol acetate). Its sensitivity was 2.2 × 10 4 C/mole, comparable to the most sensitive halo esters of steroid alcohols reported in the literature. Its electron capture coefficient was 3–7.6 × 10 10 1/mole. The coefficient was independent of the detector temperature, indicating low activation energy for electron absorption.