Synthesis and Spectral Characterization of Some Novel Phosphonyl‐ and Phosphoryl Pyrazole Compounds

1,3‐Diphenyl‐1H‐pyrazole‐4‐carbaldehyde ( 1 ) reacted with aniline, 2‐substituted anilines, and P,P‐dimethylphosphinic hydrazide in the presence of diethyl phosphite to give acyclic α‐aminophosphonate 2 , cyclic α‐aminophosphonates 4–6 , and α‐hydrazinophosphonate 7 , respectively. Also, treatment of aldehyde 1 with cyanoaceto‐hydrazide, acetophenone, and malononitrile afforded the condensation products 8 , 16 , and 21 , respectively, which in turn, reacted with diethyl phosphite and P,P‐dimethylphosphinic hydrazide. The reaction of diethyl phosphite with the hydrazone 8 and chalcone 16 yielded the novel phosphorus heterocycles 13 and 18 , respectively, while its reaction with the dicyanoarylidene 21 produced the dicyanopyrazolyl phosphonate 22 . On the other hand, treatment of the hydrazone 8 with P,P‐dimethylphosphinic hydrazide gave the unexpected P,P‐dimethylphosphinic hydrazone 15 , which reacted with diethyl phosphite forming α‐hydrazinophosphonate 7 . Furthermore, the interesting N‐phosphoryl pyrazoles 20 and 24 were resulted in good yield via cycloaddition of P,P‐dimethylphosphinic hydrazide to the chalcone 16 and dicyanoarylidene 21 , respectively. Structures of all newly synthesized compounds were confirmed by considering the data of IR spectroscopy, MS, and ¹H‐, ¹³C‐, and ³¹P‐NMR spectroscopy, as well as that of elemental analyses.     

Separation,interconversion, and insecticidal activity of the cis‐ and trans‐isomers of novel hydrazone derivatives

A series of cis‐ and trans‐isomers of hydrazone derivatives were separated and analyzed through HPLC with diode‐array detection and HPLC‐MS/MS using ESI and ion trap MS. Two single crystals (A‐5‐1 and C‐2‐1) of the trans‐isomers were obtained and determined using X‐ray crystallography data, and the cis‐ to trans‐isomerization under different conditions was discussed. Both of the cis‐ and trans‐isomers of A‐4 and A‐5 exhibited good insecticidal activities against Plutella xylostella.     

Rhodium(III)‐Catalyzed CH Activation and Indole Synthesis With Hydrazone as an Auto‐Formed and Auto‐Cleavable Directing Group

An efficient, practical, and external‐oxidant‐free indole synthesis from readily available aryl hydrazines was developed, by using hydrazone as a directing group for Rh^III‐catalyzed C?H activation and alkyne annulation. The hydrazone group was formed by in situ condensation of hydrazines and C?O source, whereas its N?N bond was served as an internal oxidant, for which we termed it as an auto‐formed and auto‐cleavable directing group (DG^auto). This method needs no step for pre‐installation and post‐cleavage of the directing group, making it a quite easily scalable approach to access unprotected indoles with high step economy. The DG^auto strategy was also applicable for isoquinoline synthesis. In addition, synthetic utilities of this chemistry for rapid assembly of π‐extended nitrogen‐doped polyheterocycles and bioactive molecules were demonstrated.     

Cycloalkene budding: mass spectrometric studies of competitive and dual cycloalkene extrusion reactions from doubly unsaturated aldehyde N,N-dimethylhydrazones

Mass spectral fragmentation pathways of four doubly unsaturated aldehyde N,N-dimethylhydrazones were investigated using EI-MS and tandem mass spectrometry (MS/MS) under electron ionization and collisionally activated decomposition (CAD) conditions. Cyclopentene extrusion was found to be slightly favored over cyclohexene loss in a hydrazone capable of losing either cycloalkene. Evidence for the regeneration of a chain-shortened iminium radical cation as a result of cycloalkene extrusion was provided by studying substrates capable of undergoing successive cycloalkene budding sequences. EI-MS of these compounds shows sequential loss of both cyclopentene and cyclohexene, in accord with expectations for a cascade mechanism. Although these MS/MS experimental results are also compatible with alternative mechanisms which would entail the simultaneous loss of both neutral cycloalkenes or of a macrocyclic diene, a rapid cascade of cycloalkene budding accounts best for the experimental observations.     

О,О‐Dialkyl‐S‐(1,1‐dimethyl‐2‐oxoethyl)dithiophosphates: Synthesis and Reactions with n‐Nucleophiles

Hydrolysis of the new types of iminium salts was used to synthesize О,О‐dialkyl‐S‐(1,1‐dimethyl‐2‐oxoethyl)dithiophosphates or 2‐dialkoxythiophosphorylthio‐substituted aldehydes with carbon isochain. Reactions of aldehydes with N‐, N,N‐, and O,N‐nucleophiles gave new phosphorylated imines containing an acetal group at different positions, perhydro‐1,3‐diazol and oxazol with the diisopropoxythiophosphorylthio group in a side chain, and hydrazone of this aldehyde and diphenylphosphinylacetic acid hydrazide.     

Synthesis of some new substituted ethanone hydrazones containing 1H‐1,2,4‐triazole and thiazole

Three new thiosemicarbazones have been synthesized by condensation reaction of 2‐bromo‐1‐arylethanones with thiosemicarbazide, which reacted with various 2‐bromo‐1‐arylethanones in ethanol under refluxing to give a series of substituted ethanone hydrazone derivatives. Their structures were confirmed by elemental analysis, IR, ¹H NMR, and MS spectra.     

Contributions to the chemistry of 3‐cyanoacetylhydrazono‐2‐indolinones and X‐ray structure of Z‐3‐cyanoacetylhydrazono‐2‐indolinone monohydrate

The tendency of acylhydrazones to undergo a spontaneous cyclization into 1,3,4‐oxadiazolines has been investigated. Contrary to the literature data, an attempted transformation of isatin cyanoacetylhydrazone in solution generates stereoisomers and not the reported structural isomer oxadiazoline. A similar behavior of the corresponding l‐methyl‐ and l‐acetylisatin derivatives even under acetylation conditions has been found. The crystal structure of the Z isomer of 3‐cyanoacetylhydrazono‐2‐indolinone monohydrate is reported. It contains strong intramolecular hydrogen bond between the hydrazone N H and oxygen atom of the indolinone carbonyl, and in this way the Z isomer over the CN bond is stabilized. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:183–193, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20531     

A new supramolecular zinc(II) complex containing 4‐biphenylcarbaldehyde isonicotinoylhydrazone ligand: Nanostructure synthesis,catalytic activities and Hirshfeld surface analysis

A new potentially tridentate hydrazone ligand, 4‐biphenylcarbaldehyde isonicotinoylhydrazone (4‐bpinh), was prepared by the condensation of biphenyl‐4‐carboxaldehyde with isonicotinic acid hydrazide. Then, its nano‐sized and single crystal of zinc complex were synthesized using sonochemical and heat gradient methods, respectively. The structure of complex, [Zn(4‐bpinh)₂ Br₂] (1), was determined by single‐crystal X‐ray diffraction, FT‐IR, and elemental analysis, and the nano‐structure of complex was characterized by FT‐IR, XRD, and SEM. The single crystal X‐ray structure of complex showed that the metal center has a distorted tetrahedral geometry and the hydrazone ligand acts as monodentate trough the pyridyl N atom. Moreover, the analysis of crystal structures indicates the existence of intermolecular interactions such as N/C–H?Br/O, N/C–H?π, and π?π stacking in the stabilization of complex structure which finally led to the formation of the three‐dimensional supramolecular structure. Also, the impact of this interactions was more studied using Hirshfeld surface analysis and corresponding 2D fingerprint plots. Furthermore, the catalytic activity of 1 was studied in the selective oxidation of various sulfides to corresponding sulfoxides using hydrogen peroxide as the oxidative agent.     

Mass spectrometric study of N‐glycans from serum of woodchucks with liver cancer

Woodchucks have been a preferred lab animal model of chronic hepatitis B viral infection. The model recapitulates the disease progression of HBV infection to hepatocellular carcinoma (HCC) and has documented similarities in protein glycosylation with human HCC. This study examined N‐glycans in serum of animals with(out) HCC. Oligosaccharides were released enzymatically using PNGaseF from total serum or from serum partially fractionated by extraction. Two different extraction procedures – reversed‐phase high‐performance liquid chromatography (RP‐HPLC) and solid‐phase extraction (SPE) on a cation‐exchange/reversed‐phase STRATA‐XC cartridge – were used with the purpose of confirming glycosylation profiles. Oligosaccharides were analyzed by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) after derivatization with phenylhydrazine and/or permethylation. Characteristic fragment ions produced under MS/MS conditions allowed discrimination between isomeric structures of oligosaccharides, including those sialylated with two types of acidic residues. The complementary methods allowed structural characterization of oligosaccharides from various N‐glycan classes. Furthermore, to validate results, glycosylation profiles of woodchuck sera were compared to glycans obtained from mouse serum on the same conditions. In summary, we have identified 40 N‐glycan structures in the serum of woodchucks and some types of oligosaccharide structures appeared to increase in HCC samples following protease digest. The study provides improved tools for the characterization of N‐glycans from total serum in the progression of liver disease. Copyright © 2009 John Wiley & Sons, Ltd.     

Structural similarities among eight benzoylhydrazones

The crystal structures of eight benzoylhydrazones with different substituents have been investigated, namely 1‐benzoyl‐2‐(propan‐2‐ylidene)hydrazone, C₁₀H₁₂N₂O, (I), 1‐benzoyl‐2‐(1‐cyclohexylethylidene)hydrazone, C₁₅H₂₀N₂O, (II), 1‐benzoyl‐2‐[1‐(naphthalen‐2‐yl)ethylidene]hydrazone, C₁₉H₁₆N₂O, (III), 1‐benzoyl‐2‐(1‐cyclohexylbenzylidene)hydrazone, C₂₀H₂₂N₂O, (IV), 1‐benzoyl‐2‐(1‐phenylbenzylidene)hydrazone, C₂₀H₁₆N₂O, (V), 1‐benzoyl‐2‐[1‐(4‐chlorophenyl)benzylidene]hydrazone, C₂₀H₁₅ClN₂O, (VI), 1‐benzoyl‐2‐(4‐hydroxybenzylidene)hydrazone methanol monosolvate, C₁₄H₁₂N₂O₂·CH₃OH, (VII), and 1‐benzoyl‐2‐(1,1‐diphenylpropan‐2‐ylidene)hydrazone, C₂₂H₂₀N₂O, (VIII). The ten molecules in the eight crystal structures [there are two independent molecules in the structures of (V) and (VI)] show similar conformations and hydrogen‐bonding patterns. The C=N—NH—C=O group is planar, but the plane of the phenyl ring of the benzoyl group is rotated by about 30° with respect to that of the keto group [except for (IV), where the groups are coplanar]. Only in the amide group of (VIII) is the N—H group syn to the C=O bond, whereas the seven other compounds exhibit the anti conformation. Unless prevented by steric hindrance, N—H...O hydrogen bonds help to stabilize the crystal structure, which leads to infinite chains or dimers depending upon the molecular conformation. The molecular packing is supported by intermolecular C—H...O interactions. In the crystal structure of (VII), the methanol solvent molecule participates in two strong hydrogen bonds and two weak C—H...O interactions, thus acting as a link between the molecular chains.     

NHC‐Pd complex based on 1,3‐bis (4‐ethoxycarbonylphenyl) imidazolium chloride: synthesis,structure and catalytic activity in the synthesis of axially chiral benzophenone hydrazone

A novel NHC–Pd complex of 1,3‐bis (4‐ethoxycarbonylphenyl) imidazolium chloride has been synthesized and characterized by ¹H NMR, ¹³C NMR, IR and X‐ray single‐crystal diffraction studies. TG analysis shows that the NHC‐Pd complex is stable under 208 °C. The catalytic activities have been explored for the synthesis of axially chiral N‐(2′‐methoxy‐1,1′‐binaphthalen‐2‐yl) benzophenone hydrazone. The result indicates that the novel NHC‐Pd complex can achieve better catalytic activity than the Pd‐phosphine catalysts in the synthesis of axially chiral N‐(2′‐methoxy‐1,1′‐binaphthalen‐2‐yl) benzophenone hydrazone.     

Quantification of intact covalently metal labeled proteins using ESI‐MS/MS

Mass spectrometric methods matured from the successful qualitative characterization of proteins in complex mixtures into methods for quantitative proteomics often based on chemical tags with stable isotope labeling. In the study presented here, we extended the application of lanthanide‐ion‐based tags from the quantification using inductively coupled plasma‐MS into the quantification of labeled intact proteins using electrospray ionization (ESI)‐MS and ESI‐MS/MS. We applied the metal chelate tag MeCAT‐iodoacetamide (IA) (1,4,7,10‐tetraazacyclododecane N,N′,N″,N″ ′‐tetra acetic acid with a IA reactive site). Labeled proteins were separated using C3‐reversed phase‐high‐performance liquid chromatography interfaced to ESI‐MS. We could prove that even large proteins were completely labeled at all available cysteine residues using MeCAT‐IA with only a small excess of reagent. Fragmentation of labeled proteins either using infrared multiphoton dissociation in Fourier transform ion cyclotron resonance‐MS or higher‐energy collision dissociation with an Orbitrap gave characteristic fragments. We used these fragments to quantify several intact proteins avoiding digestion. To demonstrate the applicability, human serum albumin was quantified in blood serum. The high‐performance liquid chromatography/ESI‐MS/MS quantification data were validated using inductively coupled plasma‐MS. Because the metal within the tag may be any of the lanthanides, multiplexing capabilities are inherent. Copyright © 2014 John Wiley & Sons, Ltd.     

Investigation of c ions formed by N‐terminally charged peptides upon collision‐induced dissociation

Peptide fragments such as b and y sequence ions generated upon low‐energy collision‐induced dissociation have been routinely used for tandem mass spectrometry (MS/MS)‐based peptide/protein identification. The underlying formation mechanisms have been studied extensively and described within the literature. As a result, the ‘mobile proton model’ and ‘pathways in competition model’ have been built to interpret a majority of peptide fragmentation behavior. However, unusual peptide fragments which involve unfamiliar fragmentation pathways or various rearrangement reactions occasionally appear in MS/MS spectra, resulting in confused MS/MS interpretations. In this work, a series of unfamiliar c ions are detected in MS/MS spectra of the model peptides having an N‐terminal Arg or deuterohemin group upon low‐energy collision‐induced dissociation process. Both the protonated Arg and deuterohemin group play an important role in retention of a positive charge at the N‐terminus that is remote from the cleavage sites. According to previous reports and our studies involving amino acid substitutions and hydrogen–deuterium exchange, we propose a McLafferty‐type rearrangement via charge‐remote fragmentation as the potential mechanism to explain the formation of c ions from precursor peptide ions or unconventional b ions. Density functional theory calculations are also employed in order to elucidate the proposed fragmentation mechanisms. Copyright © 2016 John Wiley & Sons, Ltd.     

吡啶酮系偶氮染料解离平衡的^15NNMR和IR波谱

报道了四个富氮-15吡啶酮偶氮染料的氮-15核磁共振中β-氮原子的化学位移,研究了氮-15原子和pH值之间的关联.当样品溶液从酸性转成碱性,β-氮-15原子的化学位移从366-380PPM移到500PPM,相应于从腺型到偶氮阴离子结构.根据各种pH值的化学位移可计算腺结构的含量,用IR证实了这一系列化合物的酸碱离解平衡.在酸性或中性条件下,固态化合物的二个羰基吸收,在碱性条件下变成只有一个羰基吸收峰,其它官能团的吸收峰表明了与平衡的位移的相应变化.     

Azoalkanes—novel flame retardants and their structure–property relationship

A number of symmetrical and unsymmetrical azoalkanes of the general formula R′?N = N?R and related azoxy, hydrazone as well as azine derivatives have been synthesized in order to assess their potential as novel flame retardants for polypropylene alone or in combination with commercially available flame retardants such as alumina trihydrate (ATH), decabromodiphenyl ether (DecaBDE) and tris(3‐bromo‐2,2‐bis(bromomethyl)‐propyl)phosphate (TBBPP). The experimental results show that in the series of different sized azocycloalkanes the flame retardant efficacy decreased in the following order: R = cyclohexyl > cyclopentyl > cyclobutyl > cyclooctanyl >> cyclododecanyl. Whereas in the series of aliphatic azoalkanes compounds the efficacy decreased in the following order: R = n‐alkyl > tert‐butyl > tert‐octyl. In addition, also some of the prepared azoxy, azine, and hydrazone derivatives provide flame retardancy to polypropylene films at already very low concentrations (0.25–1 wt%). Noteworthy is that in contrast to other halogen‐free radical generators, the azoalkanes are also very effective as flame retardants in polypropylene thick moldings. Interestingly, it was found that 4,4′‐bis(cyclohexylazocyclohexyl)‐methane) shows a strong synergistic effect with ATH. Thus, in the presence of 0.5 wt% of azoalkane the ATH loading could be reduced from 60 to 25 wt% and still UL94 V‐2 rating could be reached. Furthermore, the fire testing data reveal that azoalkanes show a synergistic effect with DecaBDE and when used in conjunction with very low loadings of TBBPP. Copyright © 2010 John Wiley & Sons, Ltd.     

Two azo pigments based on β‐naphthol

There has been much discussion in the literature of the azo–hydrazone tautomerism of pigments. All commercial azo pigments with β‐naphthol as the coupling compound adopt the hydrazone tautomeric form (Ph—NH—N=C) in the solid state. In contrast, the red pigments 1‐[4‐(dimethylamino)phenyldiazenyl]‐2‐naphthol, C₁₈H₁₇N₃O, (1a), and 1‐[4‐(diethylamino)phenyldiazenyl]‐2‐naphthol, C₂₀H₂₁N₃O, (1b), have been reported to be azo tautomers or a mixture of azo and hydrazone tautomers in the solid state. To prove these observations, both compounds were synthesized, recrystallized and their crystal structures redetermined by single‐crystal structure analysis. Difference electron‐density maps show that the H atoms of the hydroxyl groups are indeed bonded to the O atoms. Nevertheless, a small amount of the hydrazone form seems to be present. Hence, the compounds are close to being `real' azo compounds. Compound (1a) crystallizes with a herring‐bone structure and compound (1b) forms a rare double herring‐bone structure.     

Controlled Release of Volatile Aldehydes and Ketones from Dynamic Mixtures Generated by Reversible Hydrazone Formation

Delivery systems generated by reversible hydrazone formation from hydrazine derivatives (see Fig. 1) and carbonyl compounds in H₂O efficiently increase the long‐lastingness of volatile aldehydes and ketones (R¹R²C?O) in various perfumery applications. The hydrazones are usually obtained in an (E) configuration at the imine double bond (NHN?C) and, in the case of aliphatic acylhydrazones R′CO? NH? N?CR¹R² (R′=alkyl), as syn and anti conformers with respect to the amide bond (CO? NHN). An average free‐energy barrier of ca. 78 kJ/mol was determined for the amide‐bond rotation by variable‐temperature ¹H‐NMR measurements (Fig. 2). In the presence of H₂O, the hydrazone formation is entirely reversible, reaching an equilibrium composed of the hydrazine derivative, the carbonyl compound, and the corresponding hydrazone. Kinetic measurements carried out by UV/VIS spectroscopy showed that the same equilibrium was reached for the formation and hydrolysis of the hydrazone. Rate constants are strongly pH‐dependent and increase with decreasing pH (Table 1). The influence of the hydrazine structure on the rate constants is less pronounced than the pH effect, and the presence of surfactants reduces the rate of equilibration (Tables 1 and 3). The full reversibility of the hydrazone formation allows to prepare dynamic mixtures by simple addition of a hydrazine derivative to several carbonyl compounds. Dynamic headspace analysis on dry cotton showed that the presence of a hydrazine derivative significantly increased the headspace concentrations of the different carbonyl compounds as compared to the reference sample without hydrazine (Table 4). The release of the volatiles was found to be efficient for fragrances with high vapor pressures and low H₂O solubility. Furthermore, a special long‐lasting effect was obtained for the release of ketones. The simplicity of generating dynamic mixtures combined with the high efficiency for the release of volatiles makes these systems particularly interesting for practical applications and will certainly influence the development of delivery systems in other areas such as the pharmaceutical or agrochemical industry.     

A convenient and efficient synthesis of heteroaromatic hydrazone derivatives via cyclization of thiosemicarbazone with ω‐bromoacetophenone

The synthesis of hydrazone derivatives containing thiazole unit was achieved with condensation of thiosemicarbazones and ω‐bromoacetophenone at room temperature. This mild, convenient, and efficient method affords the desired products with good to excellent yields. Their structures have been determined by X‐ray diffractional analysis, ¹H‐NMR, MS, elemental analysis, and IR. Thiosemicarbazones were prepared by the condensation of thiosemicarbazide with aldehydes or ketones. J. Heterocyclic Chem., (2011).     

Synthesis and Characterization of Acetone Hydrazones

1‐Isopropylidene‐2‐methylhydrazine ( 1 ), 1‐isopropylidene‐2‐hydroxyethylhydrazine ( 2 ) and 1‐isopropylidene‐2‐formylhydrazine ( 3 ) were synthesized by reaction of the corresponding hydrazine with an excess of acetone in the presence of a drying agent (anhydrous sodium sulfate or barium oxide). All compounds 1 – 3 were characterized by elemental analysis, coupled gas chromatography‐mass spectrometry (GC–MS), multinuclear NMR spectroscopy (¹H, ¹³C and ¹⁵N) and vibrational spectroscopy (infrared and Raman). Compounds 1 and 2 are liquid at room conditions and their density was measured by means of a picnometer, however, (at room conditions) compound 3 is a solid and its crystal density and structure were determined by low temperature X‐ray diffraction techniques (monoclinic, P2₁/n, Z = 4, a = 5.666(1) Å, b = 6.254(1) Å, c = 15.277(4) Å, β = 91.30(2)°, V = 541.2(2) ų). The structure of hydrazone 3 is discussed in detail and compared to that of monoformylhydrazine. Finally, the (gas phase) structure of compound 3 was optimized using DFT calculations (B3LYP/6‐31+G(d, p)) and its NBO charges are reported.     

Copper‐catalyzed Cyclization of 3‐Acylcoumarin Hydrazone using Air as the Oxidant: Efficient Synthesis of Pyrazole‐Fused Coumarin Derivatives

An efficient, convenient Cu‐catalyzed formation of chromeno[4,3‐c]pyrazol‐4(1H)‐ones is reported. In this atom economic process, readily available 3‐acylcoumarin hydrazone is oxidative cyclized by direct C–N bond formation. Air has been successfully used as an oxidant, which has important economic and environmental advantages. A broad scope of 3‐acylcoumarin hydrazones can be utilized in this process.