Hydrazoic Acid Research Articles

Synthesis of Unexpected Bifunctionalized Thiazoles by Nucleophilic Attack on Allenyl Isothiocyanate

AbstractTreatment of allenyl isothiocyanate with a variety of nucleophiles leads to 5‐methylthiazoles with a functional group at the 2‐position. The same pattern of reactivity is also seen with N‐aminophthalimide. In the presence of azide salt, hydrazoic acid, or N,N‐disubstituted hydroxylamines, however, allenyl isothiocyanate is converted into bifunctionalized thiazoles. We explain the formation of these products by nucleophilic addition at the isothiocyanato moiety followed by ring closure and an N–N or N–O cleavage reaction to generate short‐lived 2‐imino‐5‐methylidenethiazole or 5‐methylidenethiazol‐2‐one. Such intermediates are trapped by addition reactions to give the final heterocyclic compounds. In the case of N,N‐disubstituted hydroxylamines, the primary addition products with allenyl isothiocyanate can be detected as unstable intermediates by IR and NMR spectroscopy.

Mathematical description of the extraction of impurity acids with tributyl phosphate in diluent and of the coextraction of the acid anions with uranyl nitrate

The distribution of pertechnetic, permanganic, chromic, oxalic, acetic, formic, hydrazoic, nitrous, hydrofluoric, and hydrochloric acids and of hydrogen peroxide is considered within the framework of a new approach to modeling of extraction equilibria involving tributyl phosphate (TBP) in diluent. The approach is similar to that used for describing the extraction of nitric acid. Namely, the formation of solvates with TBP and the dissolution of the acids in water present in the organic phase are considered. Possible dissociation and dimerization of acids in both phases and association with the nitric acid-TBP monosolvate are taken into account. The coextraction of acid anions with uranyl is described taking into account the anion exchange and complexation with acid anions in the organic phase, with such complexation also occurring in the aqueous phase. A system of 16 equations with concentration constants or experimental equilibrium parameters is suggested for describing the extraction of impurity acids and coextraction of their anions.

Use of Aziridines for the Stereocontrolled Synthesis of (−)-LL-C10037α, (+)-MT35214, and (+)-4-epi-MT35214

Strategies for the synthesis of the title compounds have been developed using a diastereoselective aziridination reaction of 4-O-substituted cyclohexenones. Aziridination using a chiral amine permitted resolution of a 4-hydroxycyclohexane derivative, and this resulted in the synthesis of both enantiomers of the title compound. Alternatively, the chiral 4-hydroxycyclohexenone starting material was derived from quinic acid. In both cases stereoselective epoxidation and opening of the aziridine ring with hydrazoic acid afforded the 2-azidocyclohexenone, which was transformed to the 2-acetamido group present in the natural product.

ChemInform Abstract: Green Chemistry: ZrOCl2·8H2O Catalyzed Regioselective Synthesis of 5‐Amino‐1‐aryl‐1H‐tetrazoles from Secondary Arylcyanamides in Water.

A green and efficient method for the synthesis of 5-amino-1-aryl-1H-tetrazoles with excellent yields and high purity from secondary arylcyanamides is described. This method is completely green because no organic solvents or protic acid catalyst is used that can generate hydrazoic acid (HN3). In addition, it is a very clean method for acquiring 5-amino-1-aryl-1H-tetrazoles without generating 5-arylamino-1H(2H)-tetrazoles in most cases.

CoFe2O4 Nanoparticles as a Magnetically Recoverable and Reusable Catalyst for the Synthesis of Arylaminotetrazoles and 5-aryloxytetrazoles

An efficient and direct method is described for the synthesis of 5-arylamino-1 H-tetrazoles (Isomer A) or 1-aryl-5-amino-1 H-tetrazoles (Isomer B) and 5-aryloxytetrazoles from arylcyanamides or cynates with nano CoFe2O4 as a reusable and efficient heterogeneous catalyst. Isomer A was obtained from arylcyanamides carrying electron-withdrawing substituents on the aryl ring, while isomer B was produced with electron-releasing groups. The significant advantages of this methodology are high yields, elimination of dangerous and harmful hydrazoic acid, simple work-up procedure and the recovery and reusability of the catalyst.

Multistage mechanism of thermal decomposition of hydrogen azide

A kinetic mechanism for combustion of hydrogen azide (HN3) comprising 61 reactions and 14 flame species (H2, H, N, NH, NH2, NNH, NH3, HN3, N3, N2H2, N2H3, N2H4, N2, and Ar) was developed and tested. The CHEMKIN software was used to calculate the flame speed at a pressure of 50 torr in mixtures of HN3 with various diluents (N2 and Ar), as well as the self-ignition parameters of HN3 (temperature and pressure) at a fixed ignition delay. The modeling results of the flame structure of HN3/N2 mixtures show that at a 25–100% concentration of HN3 in the mixture, the maximum temperature in the flame front is 25–940 K higher than the adiabatic temperature of the combustible mixture. Analysis of the mechanism shows that burning velocity of a HN3/N2 mixture at a pressure of 50 torr is described by the Zel’dovich-Frank-Kamenetskii theory under the assumption that the burn rate controlling reaction is HN3 + M = N2 + NH + M (M = HN3) provided that its rate constant is determined at a superadiabatic flame temperature. The developed mechanism can be used to describe the combustion and thermal decomposition of systems containing HN3.

Multiple Poisonings with Sodium Azide at a Local Restaurant

BackgroundSodium azide is a chemical with a mechanism similar to cyanide. There is concern that it could be used as a chemical warfare agent. ObjectivesWe report a cluster of poisonings that occurred at a public restaurant and the subsequent investigation that identified iced tea contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. Case ReportFive patients became ill within minutes of drinking iced tea at a restaurant. They all presented to the same Emergency Department with similar symptoms, and improved with fluids, antiemetics, and supportive care. A joint investigation by the Dallas County Department of Health and Human Services, the Texas State Health Department, the Dallas County Southwestern Institute of Forensic Sciences, and the medical toxicologists at the University of Texas Southwestern School of Medicine identified iced tea, contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. ConclusionThe recurrence, and seriousness, of these events suggests a need for continued education of emergency providers. Emergency physicians should consider exposures to toxic chemicals in their differential when a cluster of patients presents with similar symptoms over a short period of time.

The one-pot synthesis of 4-aryl-1H-1,2,3-triazoles without azides and metal catalization

In this study, a new methodology for the one-pot synthesis of 4-aryl-1H-1,2,3-triazoles from arylglyoxaldoxime semicarbazone is presented. 4-Aryl-1,2,3-triazoles were obtained in moderate to good yields via sodium dithionite and O2, which are all efficient, safe and inexpensive reagents. This reaction is more suitable for large-scale syntheses than those using hydrazoic acid, sodium azide, or organic azides.

Synthesis of 6H-Pyrrolo[2,3,4-gh]perimidines from naphthalene-1,4,8-triamine

The importance of indole derivatives as biologically active compounds is difficult to overestimate. Benzo[c,d]indoles are not an exception; for example, efficient inhibitors of thymidylate synthase were found among compounds of this series [1]. The present communication describes the synthesis of fused benzo[c,d]indole derivatives, 6H-pyrrolo[2,3,4-gh]perimidines IVa–IVc, from naphthalene-1,4,8-triamine (I) and 1,3,5-triazines IIa–IIc. We previously showed that 1,3,5-triazine in polyphosphoric acid (PPA) acts as efficient formylating and acylating agent [2–5], in particular toward naphthylamines [5]. Therefore, it may be expected that the use of 1,3,5-triazine should ensure convenient synthesis of pyrroloperimidines IVa–IVc. In fact, by heating triamine I with triazines IIa–IIc in PPA first at 80–90°C and then at 130–140°C we obtained the corresponding pyrroloperimidines IVa–IVc in 38–48% yield. The reaction is likely to involve intermediate formation of aminoperimidines IIIa–IIIc. Unlike the known procedure [6], the proposed method requires no preliminary preparation and acylation of perimidines. Furthermore, the key step in the known procedure [6] is the Schmidt reaction utilizing sodium azide in acid medium, and there exists a risk of evolution of toxic and explosive hydrazoic acid. The procedure proposed by us is free from the said disadvantage.

μ-Nitrido diiron octaethylporphyrin complex: synthesis and properties

μ-nitrido diiron porphyrin complex ( OEPFe )2 N (OEP = octaethylporphyrinato dianion) was synthesized by the treatment of ( OEPFe ) Cl with hydrazoic acid followed by the thermal decomposition of formed ( OEPFe ) N 3 complex. The ( OEPFe )2 N complex was investigated by UV-vis, IR, HR ESI-TOF MS and EPR spectroscopic methods. EXAFS study indicated a very short Fe – Fe distance of 3.30 Å in this dimer compared with 3.48 Å distance between iron sites in the related μ-nitrido diiron complex on the tetraphenylporphyrin platform. This difference can be explained by the steric hindrance exerted by phenyl substituents in the latter. The spectral properties of the ( OEPFe )2 N complex are discussed. The catalytic properties of ( OEPFe )2 N were evaluated in the oxidation of cyclohexene and cyclohexane.

ChemInform Abstract: The Schmidt Reaction

AbstractReview: 669 refs.

Green chemistry: ZrOCl2·8H2O catalyzed regioselective synthesis of 5-amino-1-aryl-1H-tetrazoles from secondary arylcyanamides in water

A green and efficient method for the synthesis of 5-amino-1-aryl-1H-tetrazoles with excellent yields and high purity from secondary arylcyanamides is described. This method is completely green because no organic solvents or protic acid catalyst is used that can generate hydrazoic acid (HN3). In addition, it is a very clean method for acquiring 5-amino-1-aryl-1H-tetrazoles without generating 5-arylamino-1H(2H)-tetrazoles in most cases.

Synthesis of 1-substituted Tetrazoles Using CoFe2O4 Nanoparticles as a Magnetically Recoverable and Reusable Catalyst

Nano CoFe2O4 is found to be efficient catalyst for synthesis of 1-substituted 1H-1,2,3,4-tetrazoles under solvent- free conditions. The significant advantages of this methodology are high yields, elimination of dangerous and harmful hydrazoic acid and simple work-up procedure. The catalyst was easily isolated from the reaction mixture by magnetic decantation using an external magnet and reused with no significant loss in its reactivity. Keywords: CoFe2O4 Nanoparticles, Primary amines, triethyl orthoformate, 1-substituted 1H-1, 2, 3, 4-tetrazole.

Multicomponent Ligation of Steroids: Creating Diversity at the Linkage Moiety of Bis-spirostanic Conjugates by Ugi Reactions

The diversity-oriented synthesis of novel bis-spirostanic conjugates utilizing two different Ugi four-component reactions (Ugi-4CR) is described. Spirostanic steroids were functionalized with Ugi-reactive groups, that is, amines, isocyanides, and carboxylic acids, and next were subjected to multicomponent ligation approaches leading to bis-steroidal conjugates featuring pseudo-peptidic and heterocyclic linkage moieties. Both the classic Ugi-4CR and its hydrazoic acid variant were implemented, proving good efficiency for the ligation of isocyanosteroids to spirostanic acids and equatorial amines. Axially oriented amines showed poorer results, although model studies proved that chemical efficiency could be significantly improved while increasing reaction times. Overall, the method comprises the rapid generation of molecular diversity at the bis-steroid linkage moiety and, consequently, shows promise toward the production of combinatorial libraries of bis-spirostanes for biological screening.

Accurate Study of the Two Lowest Singlet States of HN3: Stationary Structures and Energetics at the MRCI Complete Basis Set Limit

The two lowest singlet potential energy surfaces of the hydrazoic acid are explored using high-level quantum chemistry calculations, revealing isomeric forms, transition states, and a new path for the nitrogen ring-closing mechanism in the ground state. The reaction of cyc-N3 with hydrogen is shown to proceed through a barrierless path that dissociates to N2 + NH((1)Δ) without reaching the HN3 global minimum. Several intersections between the two states are localized for both N3 isomers near the N3 + H dissociation. The energies of stationary structures and dissociation asymptotes are obtained with the multireference configuration interaction method at the complete basis set limit. A comparison with recent experimental data regarding the H-N3 bond strength and the dissociation barrier in the excited state shows that the present results are of chemical accuracy (~1 kcal mol(-1)).

New data on joint extraction of actinide nitrates and some acids with tributyl phosphate diluted with paraffins and mathematical description of the process by A.M. Rozen’s Model

Published data were systematized and new data were obtained on extraction of nitric acid, nitrates of uranium, neptunium, and plutonium in various valence states, thorium nitrate, and zirconium nitrate, and also on the effect exerted on their distribution ratios by temperature and other components present in the system, with 30% TBP in paraffin diluent used as organic phase. Data on the extraction of pertechnetic, acetic, formic, hydrazoic, hydrochloric, and dichromic acids and/or on the coextraction of their anions with U(VI) and Zr were obtained. Refined equations based on A.M. Rozen’s model were suggested for mathematical description of the extraction of the above components. These equations include the concentration extraction constants as polynomial functions of the solution ionic strength and take into account changes in the phase volumes upon mass transfer. Principles of stepwise calculation of extraction cascades in the steady-state mode, with data output in the tabular form and possibility of their transfer into MS Excel, are briefly described. The user’s interface is shown, and examples of head extractor calculation are presented.

Synthesis, characterization, X-ray diffraction, antimicrobial and in vitro cytotoxicity studies of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole

Abstract The synthesis, spectral characterization, crystal structure and antimicrobial activity of the novel synthetic molecule 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole, C29H48N4 has been reported. The structure has also been determined by X-ray diffraction technique using direct method and was refined on F2 by the full-matrix least-squares. Crystals are orthorhombic and their space group is P212121, with a = 7.230(3), b = 31.451(13), c = 11.974(5) (A), α = β = γ = 90°. It can be conveniently obtained by the reaction of 7-Oxostigmast-5-ene with hydrazoic acid. The molecule has also been screened for its possible in vitro antimicrobial activity against Staphylococcus aureus, Streptococcus mutans, Streptococcus pyogenes, Staphylococcus epidermidis, Bacillus cereus, Corynebacterium xerosis, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Pseudomonas aeruginosa (MTCC 424). Minimum inhibitory concentration (MIC) of the synthesized compound has also been evaluated. The highest activity is observed against C. xerosi and P. vulgaris. Moreover, the compound has also been screened for its in vitro cytotoxicity against human colon carcinoma cell line, HCT116 and human liver hepatocellular carcinoma cell line, HepG2, using doxorubicin as standard. On the basis of its IC50 values, 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole was found to inhibit the cancer cells effectively.

A click-activated fluorescent probe for selective detection of hydrazoic acid and its application in biological imaging

Here we present a new approach to aqueous hydrazoic acid detection through the synthesis and evaluation of an alkyne-based fluorescent probe, which could be applied in the monitoring of hydrazoic acid in both living Hela cells and larval zebrafish. This probe can also serve as an early warning automaton which would alert when both azide and protons exist over the threshold value.

An Experimental and Computational Assessment of Acid-Catalyzed Azide-Nitrile Cycloadditions

The mechanism of the azide-nitrile cycloaddition mediated by different Brønsted and Lewis acids has been addressed through DFT calculations. In all cases activation of the nitrile substrate by the Brønsted or Lewis acid catalyst was found to be responsible for the rate enhancement. According to DFT calculations the cycloaddition proceeds in a stepwise fashion involving the initial formation of an open-chain imidoyl azide intermediate. Kinetic experiments performed using N-methyl-2-pyrrolidone as solvent and sodium azide as azide source demonstrate that all evaluated Brønsted acids have the same efficiency toward cycloaddition with benzonitrile, suggesting that hydrazoic acid is the actual dominant catalytic species in these tetrazole syntheses. Lewis acids such as Zn or Al salts perform in a similar manner, activating the nitrile moiety and leading to an open-chain intermediate that subsequently cyclizes to produce the tetrazole nucleus. The most efficient catalyst evaluated was 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, which can readily be generated in situ from aluminum chloride, sodium azide in N-methyl-2-pyrrolidone. The efficiency of this catalyst has been examined by preparation of a series of 5-substituted-1H-tetrazoles. The desired tetrazole structures were obtained in high yields within 3-10 min employing controlled microwave heating.

Scale-up of Azide Chemistry: A Case Study

We report research and development conducted to enable the safe implementation of a highly enantioselective palladium-catalyzed desymmetrization of a meso–bis-ester using trimethylsilylazide (TMSN3) as the nucleophile. This work is used as a case example to discuss safe practices when considering the use of azide reagents or intermediates, with a focus on the thermodynamic and quantitative analysis of the hazards associated with hydrazoic acid (HN3).