Bidentate Reagents Research Articles

Phosphorus–nitrogen compounds. Part 64. Comparative reactions of spiro and ansa (N/O) cyclotetraphosphazenes with bulky (4-fluorobenzyl) N/N and N/O donor type bidentate reagents: structure, stereogenic properties and cytotoxic activity studies

Novel inorganic–organic hybrid multiheterocyclic-spiro and ansa cyclotetraphosphazenes were synthesized. The spectral, crystallographic, and stereogenic properties, and the cytotoxic activities of the compounds were presented.

Organocatalytic Asymmetric Synthesis of Tetrahydrothiophenes and Tetrahydrothiopyrans

Tetrahydrothiophenes and tetrahydrothiopyrans are an important class of compounds both from synthetic and biological points of view and have attracted the attention of many synthetic chemists and biologists over the years. Their high synthetic utility and diverse distribution in nature have made tetrahydrothiophenes and tetrahydrothiopyrans privileged motifs in organic chemistry. The last decade has witnessed great exploration of organocatalytic domino methods for the synthesis of enantiopure tetrahydrothiophenes and tetrahydrothiopyrans containing multiple stereocentres. The application of new bidentate reagents containing sulfur moieties in the development of double Michael reactions has revolutionized their synthesis. This microreview highlights recent organocatalytic asymmetric approaches to the synthesis of tetrahydrothiophenes and tetrahydrothiopyrans and describes the advances that have been made over the years.

Bidentate reagents form cyclic organic-Cr(VI) molecules for aiding in the removal of Cr(VI) from water: density functional theory and experimental results

Hexavalent chromium, Cr(VI), in the form of chromate (CrO4 2−) or dichromate (Cr2O7 2−) is a well-described carcinogen found in the drinking water in many parts of the country at levels deemed unsafe by the U.S. Environmental Protection Agency and the World Health Organization. We report on the ability of bidentate organic molecules containing diols or diamines to capture chromate ions from aqueous sources by forming cyclic organic-Cr(VI) carbonates or ureas. After their formation, the cyclic organic-Cr(VI) molecules are readily absorbed onto granulated activated charcoal to facilitate Cr(VI) removal. Using density functional theory, E 0 values for the reactions of diols and diamines with chromate were calculated and correlated with the experimental findings of Cr(VI) removal.

Simple Efficient Routes for the Preparation of Pyrazoleamines and Pyrazolopyrimidines: Regioselectivity of Pyrazoleamines Reactions with Bidentate Reagents

Simple Efficient Routes for the Preparation of Pyrazoleamines and Pyrazolopyrimidines: Regioselectivity of Pyrazoleamines Reactions with Bidentate Reagents

Array-based discovery of aptamer pairs.

Affinity reagent pairs that recognize distinct epitopes on a target protein can greatly improve the sensitivity and specificity of molecular detection. Importantly, such pairs can be conjugated to generate reagents that achieve two-site “bidentate” target recognition, with affinities greatly exceeding either monovalent component. DNA aptamers are especially well-suited for such constructs, because they can be linked via standard synthesis techniques without requiring chemical conjugation. Unfortunately, aptamer pairs are difficult to generate, primarily because conventional selection methods preferentially yield aptamers that recognize a dominant “hot spot” epitope. Our array-based discovery platform for multivalent aptamers (AD-MAP) overcomes this problem to achieve efficient discovery of aptamer pairs. We use microfluidic selection and high-throughput sequencing to obtain an enriched pool of aptamer sequences. Next, we synthesize a custom array based on these sequences, and perform parallel affinity measurements to identify the highest-affinity aptamer for the target protein. We use this aptamer to form complexes that block the primary binding site on the target, and then screen the same array with these complexes to identify aptamers that bind secondary epitopes. We used AD-MAP to discover DNA aptamer pairs that bind distinct sites on human angiopoietin-2 with high affinities, even in undiluted serum. To the best of our knowledge, this is the first work to discover new aptamer pairs using arrays. We subsequently conjugated these aptamers with a flexible linker to construct ultra-high-affinity bidentate reagents, with equilibrium dissociation constants as low as 97 pM: >200-fold better than either component aptamer. Functional studies confirm that both aptamers critically contribute to this ultrahigh affinity, highlighting the promise of such reagents for research and clinical use.

Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of Polycyclic Pyrrole Derivatives

Several (3) new benzimidazole based polycyclic compounds of potential pharmaceutical interest have been prepared starting from 2-benzimidazolelyl (1,3-dioxo-2-indenylidene) acetonitrile. Unhypothesized, the C≡N function of the plausible intermediates was released as HCN rather than a classical nucleophilic addition when treated with bidentate reagents such as hydrazines, 5-amino-1H-1,2,4-triazole, 5-amino-4-cyano-1H-pyrazole and 2-aminobenzimidazole. When compound 3 reacted with active acetonitrile derivatives it afforded new polyfunctional pyridines via elimination of HCN in addition to, new pyrimidine, pyrazine and azepine derivatives.

Synthesis and Antibacterial Activity of Some New S-Triazole Derivatives

Alkylation of 4-anilino-5-phenyl-4H-1,2,4-triazole-3-thiol (1) with some halo compounds yielded the corresponding sulfides 2a–f. Some sulfides 2e,f were cyclized to give triazolothiadiazines 3 and 4. Triazolothiadiazoles 5 and 6 were prepared through the reaction of compound 1 with carbon disulfide or ethyl orthoformate, respectively. Treatment of compound 1 with ethyl chloroformate or phenyl isothiocyanate yielded triazolo-thiadiazole and triazole 9 and 10, respectively. Reaction of compound 1 with Lawesson's reagent gave triazolothiadiazaphosphole derivative 11. Also, compound 1 underwent cyclocondensation reactions with some bidentate reagents to give triazolothiazines 4, 12, and 13. Triazolo-thiazepines and triaziepine 14–16 were synthesized via the reaction of compound 1 with β-ketoesters or ethyl cyanoacetate. Tricyclic systems 19 and 20 were prepared through the reaction of compound 4 with the appropriate reagent. Some synthesized compounds were tested for antibacterial activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Benzimidazole Annulated New Heterocyclic Compounds: Synthesis of New Polycyclic Pyrazole Derivatives

Several (3) new benzimidazole based polycyclic compounds of potential pharmaceutical interest have been prepared starting from 2‐benzimidazolelyl (1,3‐dioxo‐2‐indenylidene) acetonitrile. Unhypothesized, the C≡N function of the plausible intermediates was released as HCN rather than a classical nucleophilic addition when treated with bidentate reagents such as hydrazines, 5‐amino‐1H‐1,2,4‐triazole, 5‐amino‐4‐cyano‐1H‐pyrazole and 2‐aminobenzimidazole. When compound 3 reacted with active acetonitrile derivatives it afforded new polyfunctional pyridines via elimination of HCN in addition to, new pyrimidine, pyrazine and azepine derivatives.

New Route Synthesis of Styryl Pyrones: High Yield Synthesis, Reactions and Spectral Properties of 2-Phenyl-6-Styryl-4-Pyrones

2-Phenyl-6-styryl-4-pyrone derivatives have been synthesised from the reaction of ethyl phenylpropiolate with benzylideneacetone derivatives in the presence of sodium ethoxide. Treatment of styrylpyrone with phosphorus pentasulfide gave the corresponding styrylpyran-4-thione which on treatment with hydroxylamine hydrochloride and aqueous methylamine afforded the corresponding oxime and 1-methyl-2-phenyl-6-styrylpyridine-4(1H)-thione, respectively. On the other hand, styrylpyran-4-thione reacted with malononitrile to give pyrolylidenemalononitrile which on treatment with bidentate reagents, hydrazine hydrate, hydroxylamine hydrochloride, thiourea, and thiosemicarbazide afforded the corresponding styrylspiropyran derivatives of pyrazole, 1,2-oxazole or 1,3-thiazine, respectively.

Synthesis of Some New Spirothiopyran Derivatives from the Reaction of 4-Thiopyrylidenemalononitriles with Bidentate and Active Methylene Reagents

2,6-Diphenyl and 2-phenyl-6-p-tolyl-4-thiopyrylidenemalomonitriles have been synthesized as f , g -unsaturated nitriles from the condensation of 2,6-diphenyl and 2-phenyl-6-p-tolyl-4H-thiopyran-4-thiones with malononitrile. Treatment of 4-thiopyrylidenemalononitriles with hydrazine hydrate, hydroxylamine hydrochloride, thiourea, thiosemicarbazide, or guanidine hydrochloride afforded the corresponding spirothiopyran derivatives of pyrazole, isoxazole, 1,3-thiazine or pyrimidine, respectively, while treatment with acetylacetone gave the corresponding spirothiopyran derivatives of pyran.

A CONVENIENT SYNTHESIS OF POLYFUNCTIONALLY SUBSTITUTED HETEROCYCLIC SYSTEMS DERIVED FROM 4-METHYL-2H-l,4- BENZOXAZIN-3-ONE

Cycloaddition of 2-|(N-phenyl)thiocarboxamido-|-4-methyl-2H,4-benzoxazin-3-one (2) to α,β-unsaturated compounds gave spiro pyridine derivatives. Reaction of compound 2 with some halo compounds afforded thiazolidine derivatives. 2-Ethoxymethylenyl-4-methyl-l.4-benzoxazine-3-thione underwent cyclocondensation reactions with some bidentate reagents. Condensed tricyclic systems have been prepared through the reaction of 3-dicyanoniethylenyl-4-methyl-2H-1,4-benzoxazine with the appropriate reagents.

Synthesis of cyclopentenones and butenolides by reaction of the lithium salt of P,P-diphenyl-P-(alkyl)(N-phenyl)phosphazenes with electrophilic double and triple bonds

Lithium P,P-diphenyl-P-(alkyl)(N-phenyl)phosphazenes act as bidentate reagents towards electrophilic olefins and acetylenes. The reactions with dimethyl acetylenedicarboxylate (DMAD) and dimethyl maleate afford cyclopentenones, while with methyl benzoylpropiolate the products obtained are butenolides with a quaternary carbon atom in position 5 of the heterocycle. The use of less activated substrates (methyl phenylpropiolate, methyl cinnamate, and dimethyl oxalate) allowed the isolation of C-acylated aminoylide or phosphazene derivatives. A reaction mechanism is proposed based on a tandem process involving the regioselective C-acylation of the carbon α to the phosphorus, followed by a cyclisation process promoted by the intramolecular Michael addition of the nitrogen of the PN linkage to an electrophilic double or triple carbon–carbon bond.

ChemInform Abstract: Synthesis of Some New Spiro Heterocycles from the Reaction of 2‐Coumarylidenemalononitrile with Active Methylene and Bidentate Reagents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Some New Spiro Heterocycles from the Reaction of 2-Coumarylidenemalononitrile with Active Methylene and Bidentate Reagents

The reaction of 2-Coumarylidenemalononitriles 1a,b with some active methylene, bidentates and ketoketene S, S or N, S acetals affords a series of new spiro heterocyclic systems.

Synthesis and application of bidentate photoaffinity cross-linking reagents. Nucleotide photoaffinity probes with two photoactive groups

Two "targeted bidentate" photoaffinity cross-linking reagents, the monoanhydride of 8-N3ADP with N-(4-(benzoyl)phenylmethyl)phosphoramide ([gamma-32P]8-N3ATP gamma BP) and the monoanhydride of 8-N3GDP with N-(4-(benzoyl)phenylmethyl)-phosphoramide ([gamma-32P]8-N3GTP gamma BP), were developed for studying the inter- and intramolecular interactions of nucleotide-binding proteins. Experiments using these bidentate reagents with two photoactive groups led to specific cross-linking: [gamma-32P]8-N3GTP gamma BP and [gamma-32P]8-N3ATP gamma BP showed intersubunit cross-linking of glutamate dehydrogenase and [gamma-32P]8-N3GTP gamma BP appeared to cross-link the alpha- and beta-subunits of tubulin. The non-azido "monodentate" versions of these reagents, the monoanhydride of ADP with N-(4-(benzoyl)phenylmethyl)-phosphoramide ([gamma-32P]ATP gamma BP) and the monoanhydride of GDP with N-(4-(benzoyl)phenylmethyl)-phosphoramide ([gamma-32P]GTP gamma BP), were also synthesized and characterized. The ability of these monodentate reagents with one photoactive group to serve as photoaffinity probes was established by photolabeling specifically the exchangeable GTP-binding domain of tubulin with [gamma-32P]GTP gamma BP and the ATP-binding domain of purified adenylate kinase and several nucleotide-binding proteins in human brain homogenate with [gamma-32P]ATP gamma BP.

Efficiency of Tetraphenylimido Diphosphate as an Extractant

Tetraphenylimido diphosphate (HA) and five other bidentate reagents containing PO and CO groups in a close vicinity to phenyl or phenoxy groups were examined as reagent for solvent extraction of some metals. Hafnium, scandium and rare earth compounds were found to easily pass from weakly acid aqueous solutions into benzene solutions of HA, whereas the other reagents investigated mostly lack this extracting power. The causes of this effect are discussed.

ChemInform Abstract: Ethyl Carboethoxyformimidate in Heterocyclic Chemistry.

AbstractReactions of the title compound (V) with a variety of bidentate reagents are studied.

Ethyl carboethoxyformimidate in heterocyclic chemistry

The reactions of ethyl carboethoxyformimidate with various bidentate reagents illustrate its usefulness as a reagent in heterocyclic chemistry.

Chloro (ethoxycarbonyl)methyleneiminium salts - versatile electrophilic intermediates for heterocyclic synthesis

The preparation of chloro(ethoxycarbonyl)methyleneiminium salts is described. The reaction of these electrophilic salts with various bidentate reagents illustrate their usefulness as intermediates for heterocyclic synthesis.