Α-halogenated Carbonyl Compounds Research Articles

Photoinduced promiscuity of cyclohexanone monooxygenase for the enantioselective synthesis of α-deuterated carbonyl compounds

The direct asymmetric synthesis of deuterium compounds has gained increasing attention. Here we report the engineered cyclohexanone monooxygenase from Acinetobacter sp. NCIMB 9871 for the synthesis of chiral α-deuterated carbonyl compounds via enantioselective reductive dehalogenation. The engineered CHMO exhibited good chemoselectivity, stereoselectivity and d-incorporation (up to 92% yield, 98% e.e. and 96% d-incorporation) toward a series of α-halogen carbonyl compounds. This method was also used for the synthesis of deuterated drugs, which demonstrated its promising application in synthetic chemistry.

Molecular modeling and docking studies of new antimicrobial antipyrine-thiazole hybrids

A series of new antipyrine incorporated thiazole derivatives having phenoxyacetamide moiety as a link bridge was synthesized. The synthetic strategy involves condensation of the precursor N -(4-antipyrinyl)-2-(4-formylphenoxy)acetamide with thiosemicarbazide followed by heterocyclization of the produced thiosemicarbazone with various α-halogenated carbonyl compounds (namely; 4-chlorophenacyl bromide, ethyl bromoacetate, 3-chloroacetylacetone and ethyl 4-chloroacetoacetate). Moreover, the quantum chemical calculations at DFT/B3LYP level were used to determine the HOMO-LUMO energies and Fukui’s indices toward nucleophilic, electrophilic and radical attacks. The investigated compounds were arranged due to HOMO-LUMO energy gap as following 6 < 5 < 7 < 3 < 2 < 4 < 8 . The synthesized antipyrinyl-thiazole hybrids were screened to evaluate their antibacterial and antifungal efficacies. Using Chloramphenicol as reference material, the synthesized antipyrinyl-thiazole hybrids were revealed a remarkable activity against S. aureus than B. subtilis , as example for Gram’s positive strains. The antipyrine-thiazole compounds 3 , 4 , 6 and 8 exhibited significant MIC values. However, the antipyrine-thiazole hybride 4 displayed reputable activities against Gram’s negative strains S. typhimurium and E. coli , respectively, in comparison with Cephalothin. Likewise, the compounds 7 and 8 were demonstrated respectable antifungal efficacy toward C. albicans in contrast to cycloheximide grade. The theoretical molecular docking studies were applied to simulate reactivity of the synthesized antipyrine-thiazole hybrids against contrasting binding sites for both of Staphylococcus aureus “Homo sapiens” (pdb: 3HUN) protein and E.coli “Homo sapiens” (PDB: 2EXB) protein. The theoretical and practical antibacterial and antifungal activities result in this work designated a proper agreement.

Synthesis and antiproliferative activity studies of new functionalized pyridine linked thiazole derivatives

Ten new pyridine linked various substituted thiazole hybrids through (hydrazonomethyl)phenoxy-acetamide spacer were synthesized. The synthetic strategy was based on the reaction of the precursor 2-(4-((2-carbamothioylhydrazono)methyl)phenoxy)-N-(pyridin-2-yl)acetamide (3) with various α-halogenated carbonyl compounds (namely; phenacyl bromides, ethyl bromoacetate, diethyl bromomalonate and 3-chloropentane-2,4-dione). Moreover, the cytotoxicity properties of the synthesized compounds have been studied against liver carcinoma (HepG2), laryngeal carcinoma (Hep-2), prostate cancer (PC3), breast cancer (MCF-7) and normal fibroblast cells (WI38). The pyridine-thiazole compounds 7 and 10 revealed promising anticancer activity against MCF-7 and HepG2 cell lines with IC50 values in the range 5.36–8.76 μM compared to the activity of 5-fluorouracil. Docking study provided valuable insights for binding sites of the synthesized compounds with Rho-associated protein kinase (ROCK-1).

α-Halo Amides as Competent Latent Enolates: Direct Catalytic Asymmetric Mannich-Type Reaction.

α-Halogenated carbonyl compounds are susceptible to dehalogenation and thus largely neglected as enolate precursors in catalytic enantioselective C-C bond-forming reactions. By merging the increased stability of the α-C-halogen bond of amides and the direct enolization methodology of the designed amide, we explored a direct catalytic asymmetric Mannich-type reaction of α-halo 7-azaindoline amides with N-carbamoyl imines. All α-halo substituents, α-F, -Cl, -Br, -I amides, were tolerated to provide the Mannich-adducts in a highly stereoselective manner without undesirable dehalogenation. The diastereoselectivity switched intriguingly depending on the substitution pattern of the aromatic imines, which is ascribed to stereochemical differentiation based on the open transition-state model. Functional group interconversion of the 7-azaindoline amide moiety of the Mannich-adducts and further elaboration into a diamide without dehalogenation highlight the synthetic utility of the present protocol for accessing enantioenriched halogenated chemical entities.

A FACILE SYNTHESIS AND REACTIONS OF AMINO SELENOLO[2,3-b]PYRIDINE CARBOXYLATE

Incorporating selenium metal bonded to the pyridine nucleus was achieved by the reaction of selenium metal with 2-chloropyridine carbonitrile 1 in the presence of sodium borohydride as reducing agent. The resulting non isolated selanyl sodium salt was subjected to react with various α-halogenated carbonyl compounds to afford the selenyl pyridine derivatives 3a-f which compounds 3a-d underwent Thorpe-Ziegler cyclization to give 1-amino-2-substitutedselenolo[2,3-b]pyridine compounds 4a-d, while the other compounds 3e,f failed to be cyclized. Basic hydrolysis of amino selenolo[2,3-b]pyridine carboxylate 4a followed by decarboxylation furnished the corresponding amino selenolopyridine compound 6 which was used as a versatile precursor for synthesis of other heterocyclic compound 7-16. All the newly synthesized compounds were established by elemental and spectral analysis (IR, 1H NMR) in addition to mass spectra for some of them hoping these compounds afforded high biological activity.

Synthesis of novel 1‐substituted [1,3]thiazolo[3,2‐a]‐[1,5]benzodiazepine derivatives from 1,5‐benzodiazepine‐2‐thiones and α‐halogen carbonyl compounds

Abstractmagnified imageA number of substituted 4H,5H,6H‐thiazolo[3,2‐a][1,5]benzodiazepinium salts 2a‐h, 5, 9, which are based on the novel thiazolobenzodiazepine system, were prepared by condensation‐cyclization of 1,5‐benzodiazepine‐2‐thiones 1a‐f, h, 4 with α‐haloketones, as well as with α‐bromoacetaldehyde diethyl acetal. The structure and stereochemistry of the ring system obtained were investigated by 1H and 13C nmr spectroscopy: the additional heterocyclic nucleus was found to appreciably influence the conformational mobility of the heptatomic ring. Upon treatment of salt 2d with alkali the presence of the base enamine structure in solution has been postulated.

Orthoamide. IL. Umsetzungen von Orthoamid-Derivaten mit Schwefel und Selen, Synthesen von 1,3-Thiazol- und 1,3-Selenazolderivaten

Orthoamides. IL. Reactions of Orthoamide Derivatives with Sulfur and Selenium, Syntheses of 1,3-Thiazole- und 1,3-Selenazole Derivatives N,N-Dimethylformamide acetal reacts with elemental selenium to give a mixture of selenocarbonic acid derivatives 2 and 3, which can be converted to the pure N,N-dimethylcarbamidic acid Se-methylester 2 by treatment with methyl iodide. Analogously from the orthoformic acid derivatives 5 and 6 and selenium the N,N,N′,N′-tetramethyl-selenurea 7 can be prepared. In the reaction of 12 with elemental sulfur and selenium the amidines 14 and 15, respectively, are formed. By treatment of 14 and 15 with α-halogenated carbonyl compounds and triethylamine the 1,3-thiazoles 18 and 1,3-selenazoles 19 can be prepared. The synthesis of the propynoic acid orthoamide 26b is described. 26b reacts with the guanidinium salt 24b to give the bis-orthoamide of butynedioic acid 20b. Other orthoamides of butynedioic acid 20b–20e can be synthesized from the orthoamide 20a by transamination. The thiolation of the orthoamides affords the bisamidinium-dithiolates 21a–c, which can be alkylated to give the bisamidinium salts 27. By treatment with α-halogene carbonyl compounds and triethylamine the dithiolates 21a–c are cyclized to give thieno [3,2b] thiophenes 28a–n. The quadrupoles 21 undergo cycloadditions with dimethyl-butynedioate which afford the bis(3H-thiophene-2-ylidenes) 29a–c. Treatment of 29a with methyl tosylate gives rise to the dithiophene 30a. The dithiophene 30b can be obtained by heating 21b with dimethylbutynedionate.

Zur Synthese von 3-Amino-pyrrolen durch Thorpe-Ziegler-Cyclisierung

On the Synthesis of 3-Amino-pyrroles by Thorpe-Ziegler-Cyclization N-Aryl and alkylaminomethylene cyanacetic acid derivatives 1 react with α-halogencarbonyl compounds 2 in the presence of potassium carbonate/sodium ethoxide to yield the substituted 3-amino-pyrroles 6. Using the same principle of cyclization pyrrole derivatives 6 can also be obtained by reaction of β-chloro- and β-alkoxymethylenemalononitriles 4 with β-aminocarbonyl compounds 5. From the malononitrile derivatives 1 containing the methylthio group in the β-position, and α-halogen ketones 7, the 2-dicyanomethylene oxazolines 8 arise which undergo alkoholysis by treatment with sodium alkoxide to form the 3-amino-5-alkoxy-pyrrole derivatives 9.

Addition products of hydrazine derivatives to azo-alkenes - III. α-phenylhydrazino-phenylhydrazones

The addition of phenylhydrazine to phenylazo-alkenes 4 yields α-(1-phenylhydrazino)-phenylhydrazones 1 . The reaction of phenylhydrazine with α-halogenated carbonyl compounds 5 affords either 1 or the isomeric α-(2-phenylhydrazino)-phenylhydrazones 2 . Structures 1 and 2 (>N-NH 2 and-NH-NH- groups, respectively) can be differentiated by 1H NMR in DMSO-D 6 solution. Possible pathways of the reactions leading to either 1 or 2 are discussed. Compounds 1 are found to be precursors of phenylosazones 6 .

Nouvelles voies d'accès aux benzopyrannes—III: 2H-benzo(b)pyrannes(chromènes-3)

Alkylation of o-hydroxybenzyl triphenylphosphonium salts with α-halogenated carbonyl compounds, in presence of base, gives chrom -3 enes.

4-Amino-1-arylpyrazole durchThorpe-Cyclisierung

α-Arylhydrazononitriles1 react with α-halogen carbonyl compounds in presence of K2CO3 to yield substituted4-amino-1-aryl-pyrazoles3. Pyrazolo[4,3-d]pyrimidines, pyrazolo[4,3-d]oxazinones and substituted 4-aminopyrazolecarboxylic acids can be obtained from3; the carboxyl group in the 5-position can be removed.

�ber einige Umsetzungen von 2,5-Diamino- sowie 2-Amino-1,3,4-thiadiazolen mit ?-Halogenketonen zu Imidazo[2,1-b]-1,3,4-thiadiazolen

2,5-Diamino-1,3,4-thiadiazole (1) reacts with α-halogencarbonyl compounds to 2-imino-3-phenacyl(acetonyl)-5-amino-1,3,4-thiadiazolines (3) which easily can be cyclised to 2-amino-6-aryl (alkyl)-imidazo[2,1-b]-1,3,4-thiadiazoles (4), the structure of which was proofed. On the basis of the amino function in position 2 these substances were able to form easilySchiff bases (5, 6, 7). Their semicyclic amidine system did not allow as yet to integraet it in a third ring system.

4-Amino-imidazoles by thorpe-cyclization

The alkylation of arylaminomethylenecyanamides1 or cyano-imidothiocarbamates2 with α-halogen carbonyl compounds followed by base catalysed cyclization yields substituted 4-amino-imidazoles4. Imidazo[4,5-d]pyrimidones5, 6 and imidazo[4,5-b]pyridines7 can be obtained from4.

Stable sulphonium phenacylides: Isolation and reactions

Methylphenylsulphonium phenacylide (II) was isolated as a stable solid upon treatment of methylphenacylphenylsulphonium bromide (I) with bases. No evidence supporting the proposed intermediacy of benzoylcarbene, which was postulated to be formed by thermal decomposition of II and then transformed into 1,2,3-tribenzoylcyclopropane (IV), was obtained, but the reaction of II with I or phenacyl bromide give IV. The ylide II reacted with certain α,β-unsaturated or α-halogenated carbonyl compounds and yielded cyclopropane derivatives (IV, XI–XIII). Treatment of the ylide II with phenyl isocyanate or acid anhydrides resulted in C-acylation affording novel stabilized ylides (XIV–XVI, Table 1), while reaction with acyl halides yielded O-acylated products (XVII, XVIII). Attempted resolution of II and p-iodo derivative (VIII) failed.

863. Infrared spectra and polar effects. Part VII. Dipolar effects in α-halogenated carbonyl compounds

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