Hydrazine Reagents Research Articles

Hydrazine reagents as derivatizing agents in environmental analysis--a critical review.

Hydrazine reagents are a well-known group of derivatizing agents for the determination of aldehydes and ketones in liquid and gaseous samples. Within this article, the most important hydrazine reagents are critically summarized, and their major applications in different fields, including environmental analysis, food chemistry and industrial analysis are introduced. As 2,4-dinitrophenylhydrazine (DNPH) is the basic reagent for several international standard procedures, its properties are discussed in detail. Particular focus is directed on the chemistry of the hydrazine reagents, and chemical interferences are considered. Recent methods for the determination of various oxidants using hydrazine reagents are presented as well. Due to limited space, this review does not cover the related field of carbohydrate analysis, although many chemical aspects are similar.

Experiments related to the synthesis and analysis of a hydrazine library †

Substitutions under competition conditions are performed with a triprotected hydrazine reagent A as nucleophile and various halides as electrophiles and the product distribution determined by HPLC. Subsequently, after partial deprotection, stepwise substitution on the other nitrogen is studied similarly in order to define the scope of such reagents for the synthesis of libraries comprising multisubstituted hydrazines. In the course of this work a large number of partially protected hydrazine derivatives are prepared and characterized spectroscopically and chromatographically. The results indicate that n-alkyl and benzyl halides are of comparable reactivity under the conditions used, whereas others deviate too much in this respect as a result of which product mixtures severely distorted from equimolar ones are formed. In the course of this work, hydrazine libraries containing up to nine components are characterized quantitatively.

Synthesis of Hydrazines with Aromatic Substituents Using Triarylbismuth Reagents

Smooth monoarylation of two triprotected hydrazine reagents under mild conditions has been accomplished using triaryl-bismuthanes in the presence of copper acetate and amine to give products 3 and 6 in excellent yield. Arylation on N-2 after selective dep

Determination of carbonyl compounds in waters using triazine-based hydrazine reagents and liquid chromatography

Triazine-based hydrazine reagents have been developed and applied for the determination of aldehydes in waters. N-Methyl-4-N′,N′-dimethylamino-6-(4 ′-methoxy-1′-naphthyl)-1,3,5-triazine-2-hydrazine (MDMNTH) and 4-N,N-dimethylamino-6-(4′-methoxy-1′-naphthyl)-1,3,5- triazine-2-hydrazine (DMNTH) react with these carbonyl compounds with very high yields under the formation of the respective hydrazones, which are separated by reversed-phase liquid chromatography with binary gradients of acetonitrile and water. Organic modifiers are added to obtain improved peak shapes. UV/vis as well as fluorescence detection has been applied successfully to quantify the hydrazones. The derivatization of aqueous solutions of the aldehydes has been optimized. Limits of detection are in the range between 0.1 μM and 1.0 μM depending on the analyte and the reagent used for derivatization. Although calibration via external standards is possible for higher analyte concentrations, best results are obtained by calibration via the derivatization reaction. Compared to the US EPA method 8315A, the newly developed method is characterized by very easy sample preparation, lower limits of detection without enrichment and excellent reproducibility with an average RSD of 1.5% with DMNTH as reagent and 3.5% with MDMNTH as reagent for a formaldehyde concentration of 1.0 ×10−5 mol L−1. Aldehyde-spiked mineral water samples were analyzed successfully with the new method.

Ultrasound assisted synthesis of pyrazole fatty ester derivatives from a key C 18 keto-allenic ester

A conjugated C 18 keto-allene ester was prepared starting from methyl ricinoleate (the main component of castor oil). Bromination-dehydrobromination of methyl ricinoleate gave methyl 12-hydroxy-9-octadecynoate. Chromic acid oxidation of the latter gave methyl 12-oxo-9-octadecynoate, which was isomerized with aqueous NaHCO 3 to yield a conjugated C 18 keto-allene ester (methyl 12-oxo-9,10-octadecadienoate). The latter compound was reacted with hydrazine, methyl hydrazine and phenyl hydrazine in methanol under concomitant ultrasonic irradiation to give methyl 9-[3(5)-hexyl-1 H-pyrazol-5(3)-yl]-nonanoate ( 3, 83% yield), methyl 9-[5-hexyl-1- N-methyl-pyrazol-3-yl]-nonanoate ( 4, 52%) and methyl 9-[5-hexyl-1- N-phenyl-pyrazol-3-yl]-nonanoate ( 5, 86%), respectively. The study revealed that the nucleophilic attack of the keto-allenic substrate was initiated by the less hindered (less substituted) nitrogen of the hydrazine reagent, which attacked the central atom of the keto-allene system. A subsequent attack of the carbonyl carbon atom by the remaining nitrogen of the hydrazine was followed by the elimination of a molecule of water to give the pyrazole nucleus. The structures of the pyrazole products ( 3–5), including that of the key C 18 keto-allene substrate ( 2), were identified by infrared, NMR spectroscopy and mass spectrometry.

Fabrication of a weakly basic chemisorption fibre with aliphatic amino groups

The conditions for fabrication of an anion-exchange fibre with primary and secondary amine groups by preliminary treatment of Nitron fibre with an aqueous solution of hydroxylamine. The effect of the chemical nature of aminating reagents—hydrazine hydrate, ethylenediamine, and triethylenetetramine—on formation of aliphatic amine groups in Nitron fibre was investigated. It was hypothesized that the kinetics of amination is a function of the basicity of the aminating reagent.

Workplace monitoring of oximes using 2,4-dinitrophenylhydrazine-coated silica gel cartridges and liquid chromatography

A liquid chromatographic (LC) method for the determination of oximes in air samples using pre-column derivatization with a hydrazine reagent has been developed. Air samples are drawn over a 2,4-dinitrophenylhydrazine (DNPH)-coated silica gel cartridge to form the corresponding hydrazones. The acid coating of the tubes and the flow rate of the air sample have been selected considering the chemical characteristics of the oximes to avoid Beckmann rearrangement or incomplete recovery. The hydrazones are separated by LC with UV/Vis detection at 365 nm. Calibration is performed externally using the stable hydrazone standards. The limit of quantification is 0.5 pmol absolute for 2-butanone oxime (corresponding to 15.0 ng/l in a 2 l air sample) and cyclohexanone oxime (corresponding to 19.5 ng/l in a 2 l air sample), respectively. Real samples from industrial workplaces have successfully been analysed using this method.

N-Methyl-4-hydrazino-7-nitrobenzofurazan as a New Reagent for Air Monitoring of Aldehydes and Ketones

The synthesis of N-methyl-4-hydrazino-7-nitrobenzofurazan (MNBDH) and its application as a new reagent for the determination of aldehydes and ketones are described. MNBDH reacts with carbonyl compounds in acidic media to the corresponding MNBD-hydrazones. In contrast to the established reagent 2,4-dinitrophenylhydrazine (DNPH), MNBDH is oxidized by both ozone and nitrogen dioxide quantitatively to only one product, N-methyl-4-amino-7-nitrobenzofurazan (MNBDA). This can easily be separated from the hydrazones of lower aldehydes by means of HPLC. Due to larger molar absorptivities and absorption maxima at wavelengths over 470 nm, selectivity is higher and limits of detection are lower for the new reagent compared to DNPH. MNBDH reacts slightly faster than DNPH with carbonyl compounds and significantly faster than other N-alkylated hydrazine reagents.

Novel Aluminum-Containing Ring Systems: An Octanuclear Structural Analogue of a Calix[4]pyrrole.

Depending on the hydrazine reagent, Me3 Al reacts to afford novel aluminum-containing macrocyclic ring structures. The reaction of Me3 Al with Me2 NNH2 provides the octanuclear calix[4]pyrrole-like 1, while under analogous conditions the reaction with MePhNNH2 gives a tetranuclear complex. Both complexes are formed by incorporation of acetonitrile.

Efficient isolation of the rare diarrhoeic shellfish toxin, dinophysistoxin-2, from marine phytoplankton

The rare diarrhoeic shellfish poisoning (DSP) toxin, dinophysistoxin-2 (DTX-2), which is an okadaic acid (OA) isomer, has been isolated from a marine phytoplankton biomass that consisted mainly of Dinophysis acuta. Using a large double plankton net (length 5.9 m), bulk phytoplankton samples were collected off the south–west coast of Ireland and extracted with methanol and chloroform. Liquid chromatography coupled with ionspray mass spectrometry and tandem mass spectrometry (LC–MS, LC–MS–MS) showed the sample contained DTX-2 and OA, at a concentration of 80 pg/cell and 60 pg/cell, respectively. Flash chromatography using silica, sephadex LH20 and C 18-silica, followed by preparative reversed-phase LC, separated DTX-2 from OA. The efficiency of the separation procedures was substantially improved by the use of a bioscreen to detect DSP toxins in eluate fractions and the application of a new derivatisation procedure for the chromatographic elucidation of toxin profiles with fluorimetric detection (LC–FLD). Thus, 1/1000th aliquots of eluate fractions were assayed using protein phosphatase-2A for the presence of inhibitory compounds. Positive fractions were further analysed for DSP toxins by LC–FLD following derivatisation using the hydrazine reagent, luminarine-3. The identity and purity of the free isolated DTX-2 was confirmed using flow injection analysis (FIA) and liquid chromatography (FIA–MS, LC–MS and LC–MS–MS).

Determination of carbonyls using liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization

A liquid chromatographic method for the determination of aldehydes and ketones based on mass spectrometric detection is described. Recently developed modular derivatizing agents are employed for analysis. These hydrazine reagents, e.g. 4-dimethylamino-6-(4-methoxy-1-naphthyl)-1,3,5-triazine-2-hydrazine (DMNTH), react with the carbonyl compounds with the formation of the respective hydrazones, which are separated by HPLC-MS with atmospheric pressure chemical ionization in the positive mode. Electrospray ionization may also be used for analysis. Particular focus is directed on various calibration approaches, including external calibration with standard solutions and internal calibration with a hydrazone standard of cyclobutanone, an aldehyde not likely to occur in real samples. A second approach for internal calibration is based on the 13C2-labelled acetaldehyde hydrazone standard. Different calibration approaches may then be used for the analysis of real samples. Limits of detection range from 2 x 10(-8) to 5 x 10(-8) mol L-1 for a series of hydrazones, including hydrazones of saturated aldehydes with alkyl chain lengths from 1 to 7 carbon atoms, and hydrazones of selected unsaturated and aromatic aldehydes as well as ketone hydrazones.

Superoxide Dependence of the Toxicity of Short Chain Sugars

Erythrose inhibited the growth of a sodA sodB strain of Escherichia coli under aerobiosis; but did not inhibit anaerobic growth of the sodA sodB strain, or the aerobic growth of the superoxide dismutase (SOD)-competent parental strain. A SOD mimic protected the sodA sodB strain against the toxicity of erythrose as did the carbonyl-blocking reagents hydrazine and aminoguanidine. Three carbon sugars, such as glyceraldehyde and dihydroxy acetone, and the two carbon sugar glycolaldehyde, were similarly toxic in an O-2-dependent manner. An unidentified dialyzable component in E. coli extract augmented the oxidation of short chain sugars, and this was partially inhibitable by SOD. The toxicity of the short chain sugars appears to be because of an O-2-dependent oxidation to alpha, beta-dicarbonyl compounds. In keeping with this view was the O-2-independent toxicity of methylglyoxal.

ChemInform Abstract: Synthesis, Application and Scope of a New Protected Hydrazine Reagent.

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, application and scope of a new protected hydrazine reagent

A novel triprotected hydrazine reagent, 1,2-Boc 2-2-Z-hydrazine ( 3),-has been made and investigated with respect to stepwise alkylation/acylation and intermediary deprotection in order to prepare multisubstituted hydrazine derivatives. Alkylation of 3 requires particularly mild basic conditions. Regiospecific cleavage of one Boc-group with acid in monoalkylated product 4 is difficult but can be accomplished with catalytic amounts of Mg(ClO 4) 2 in MeCN at 50 °C in 15 min, furnishing 5 which can easily be alkylated to 6. This product has recently been converted to fully substituted derivatives 7.

1-Methyl-1-(2,4-dinitrophenyl)hydrazine as a New Reagent for the HPLC Determination of Aldehydes

The synthesis and first application of an N-alkylated hydrazine reagent for the HPLC determination of aldehydes and ketones is described. 1-Methyl-1-(2,4-dinitrophenyl)hydrazine (MDNPH) reacts with aldehydes to give the corresponding hydrazones in the presence of an acid as catalyst. In contrast to other hydrazine reagents, MDNPH is oxidized by both ozone and nitrogen dioxide quantitatively to N-methyl-2,4-dinitroaniline (MDNA), which can be separated from the hydrazones of the lower aldehydes by means of HPLC. Unexpected elution orders are observed for the 1-methyl-1-(2,4-dinitrophenyl)hydrazones compared to those of 2,4-dinitrophenylhydrazones. Dual-wavelength detection is employed as a means for identification of different groups of the hydrazones and MDNA.

Use of Benzoyl Hydrazine Reagent for Monosaccharide Determination by High Performance Capillary Electrophoresis

Benzoyl hydrazine derivatives of reducing carbohydrates were analyzed by high performance capillary electrophoresis with on-tube ultraviolet detection. The derivatives of 9 reducing monosaccharides were completely separated in ca. 30 min. using a capillary tube (50 μm i.d., 62 cm) and 200 mM borate buffer, pH 10.8, as carrier. On-column UV detection at 220 nm was able to achieve sensitive detection down to 30‐40 femtomole levels. The experimental parameters for optimum precolumn are discussed along with derivatization and separation. It was demonstrated that this method allows quantification of reducing carbohydrates with high accuracy and reproducibility.

Stepwise synthesis of tetrasubstituted hydrazines

A new triprotected hydrazine reagent has been made and applied in alkylation/acylation reactions for stepwise synthesis of tetrasubstituted derivatives in high purity and yield.

ChemInform Abstract: Enantioselective Synthesis of Protected α‐Hydroxy Aldehydes and Ketones via Hydroxylation of Metalated Chiral Hydrazones.

Abstract α-Benzyloxy aldehydes and α-acetoxy ketones 4 of high enantiomeric purity are prepared in good overall yields via oxaziridine mediated hydroxylation of chiral hydrazone azaenolates. As auxiliaries novel proline derived hydrazine reagents 5 are used.

Identification of crotonaldehyde as a hepatic microsomal metabolite formed by alpha-hydroxylation of the carcinogen N-nitrosopyrrolidine.

Crotonaldehyde (2-butenal), which reacts with DNA and is mutagenic and carcinogenic, was identified as a hepatic microsomal metabolite of the hepatocarcinogen N-nitrosopyrrolidine. Incubation mixtures of N-nitrosopyrrolidine, cofactors, and hepatic microsomes from Aroclor pretreated or control F344 rats were derivatized with (2,4-dinitrophenyl)hydrazine reagent and the resulting mixtures analyzed by high-performance liquid chromatography. Crotonaldehyde (2,4-dinitrophenyl)hydrazone was identified by its retention time in two different systems and by its ultraviolet and mass spectrum. The ratio of 4-hydroxybutyraldehyde, which has previously been identified as a metabolite of NPYR, to crotonaldehyde was 1.5-2 over a range of substrate concentrations. The approximate values of Km and nu max for crotonaldehyde were 5.8 mM and 0.6 nmol/min/mg of protein and for 4-hydroxybutyraldehyde 14.1 mM and 1.7 nmol/min/mg of protein, for substrate concentrations between 1 and 8 mM, with microsomes from Aroclor pretreated rats. The ratio of 4-hydroxybutyraldehyde to crotonaldehyde was 1.9 upon esterase-catalyzed solvolysis of alpha-acetoxy-N-nitrosopyrrolidine, a stable precursor to the initial product of N-nitrosopyrrolidine alpha-hydroxylation. These results demonstrate that crotonaldehyde is formed upon metabolic alpha-hydroxylation of N-nitrosopyrrolidine and suggest that it may be involved in N-nitrosopyrrolidine-macromolecule interactions.

Enantioselective synthesis of protected α-hydroxy aldehydes and ketones via hydroxylation of metalated chiral hydrazones

α-Benzyloxy aldehydes and α-acetoxy ketones 4 of high enantiomeric purity are prepared in good overall yields via oxaziridine mediated hydroxylation of chiral hydrazone azaenolates. As auxiliaries novel proline derived hydrazine reagents 5 are used.