Hydrazoic Acid Research Articles

ChemInform Abstract: First Example of the Interaction of Fullerene C60 with Hydrazoic Acid.

AbstractThe first one‐pot synthesis of N‐unsubstituted aziridino‐ and triazolinofullerenes is achieved via cycloaddition of fullerene C60 and hydrazoic acid under thermal as well as photochemical reaction conditions.

Carbohydrate–steroid conjugation by Ugi reaction: one-pot synthesis of triple sugar/pseudo-peptide/spirostane hybrids

The one-pot synthesis of novel molecular chimeras incorporating sugar, pseudo-peptide, and steroidal moieties is described. For this, a new carbohydrate–steroid conjugation approach based on the Ugi four-component reaction was implemented for the ligation of glucose and chacotriose to spirostanic steroids. The approach proved wide substrate scope, as both mono and oligosaccharides functionalized with amino, carboxy, and isocyano groups were conjugated to steroidal substrates in an efficient, multicomponent manner. Two alternative strategies based on the hydrazoic acid variant of the Ugi reaction were employed for the synthesis of tetrazole-based chacotriose–diosgenin conjugates resembling naturally occurring spirostan saponins. This is the first time that triple sugar/pseudo-peptide/steroid hybrids are produced, thus opening up an avenue of opportunities for applications in drug discovery and biological chemistry.

Suicidal sodium azide intoxication: An analytical challenge based on a rare case

Intentional absorption of sodium azide is exceptional but remains extremely life-threatening because death rapidly occurs when significant doses are absorbed, either due to the direct effect of sodium azide or an indirect effect due to nitric oxide, cyanide ions or hydrazoic acid production from sodium azide. The body of a laboratory assistant, was discovered by his colleagues in the laboratory, seated on a chair located near a digital computer displaying information about sodium azide. Moreover, a half empty 99% sodium azide flask was found near the corpse. The laboratory staff confirmed that the young man was still alive 5h prior to discovery. Postmortem examination did not show any cutaneous signs of injury due to a defensive struggle. Bilateral ungual cyanosis was observed as well as a major cerebral edema and visceral congestion on autopsy. The elevated sodium azide concentration found in the gastric sample and the amount of gastric content allowed to conclude that sodium azide intake was more than 6g which was above the lethal dose, i.e. approximately 1g. Surprisingly, no sodium azide was found either in blood and serum, or in hepatic and renal tissue samplings. However, major concentrations were observed in the gastric contents, bile and urinary samples, as well as in cardiac and cerebral tissues samples. No other toxic element was found. Therefore, the post-mortem findings, the autopsy and the analytical results suggested that the laboratory assistant died after an intentional sodium azide ingestion. Sodium azide poisoning by ingestion has to date remained extremely rare and our case highlights the extreme lability of sodium azide as it was absent in the blood, in spite of significant concentrations in stomach content and some tissues. Therefore, the necessity of multiple tissues samples during autopsy should be underlined.

Two-Step Flow Synthesis of N-(2-Amino-ethyl)acylamides from Oxazolines

Key words flow chemistry - ring opening of oxazolines - hydrazoic acid - hydrogenation

Safe Scale-Up of Processes Containing Hazardous Species in the Headspace with Inline IR

Inline IR has been applied to evaluate the scale-up of processes that potentially generate hazardous diborane, hydrazoic acid, methyl chloride, or acetylene in the headspace of reactors. In addition, a new, simplified approach to calibrate the online IR analyzer for the measurement of hydrazoic acid in the gas phase has been described.

Safe Generation and Synthetic Utilization of Hydrazoic Acid in a Continuous Flow Reactor

Abstract Hydrazoic acid (HN3) was used in a safe and reliable way for the synthesis of 5-substitued-1H-tetrazoles and for the preparation of N-(2-azidoethyl)acylamides in a continuous flow format. Hydrazoic acid was generated in situ either from an aqueous feed of sodium azide upon mixing with acetic acid, or from neat trimethylsilyl azide upon mixing with methanol. For both processes, subsequent reaction of the in situ generated hydrazoic acid with either organic nitriles (tetrazole formation) or 2-oxazolines (ring opening to β-azido-carboxamides) was performed in a coil reactor in an elevated temperature/pressure regime. Despite the explosive properties of HN3, the reactions could be performed safely at very high temperatures to yield the desired products in short reaction times and in excellent product yields. The scalability of both protocols was demonstrated for selected examples. Employing a commercially available benchtop flow reactor, productivities of 18.9 g/h of 5-phenyltetrazole and 23.0 g/h of...

Synthesis of Chondramide A Analogues with Modified β‐Tyrosine and Their Biological Evaluation

Starting from cinnamates 9, obtained by Wittig reaction or Heck coupling, the diols 17 were prepared by asymmetric dihydroxylation. This was followed by a regioselective substitution of the 3-OH group with hydrazoic acid under Mitsunobu conditions. Methylation of the 2-OH group and reduction of the azide group led to the β-tyrosine derivatives 8. Condensation with the dipeptide acid 6 furnished the tripeptide part of the chondramides. The derived acids 21 were combined with the hydroxy ester 7 to the esters 22. Cleavage of the tert-butyl groups and intramolecular lactam formation gave rise to the chondramide A analogues 2 b-k. Growth inhibition assays showed most of the analogues to be biologically active. Some of them even reach the activity of jasplakinolide. It can be concluded that the 4-position of the aryl ring in the β-tyrosine of chondramide A tolerates structural modifications quite well.

First example of the interaction of fullerene C60 with hydrazoic acid

The one-pot synthesis of unsubstituted aziridinofullerene and triazolinofullerene was performed for the first time via the cycloaddition of fullerene C60 with hydrazoic acid, which was generated in situ by the reaction of NaN3 with H2SO4.

ChemInform Abstract: Menthone and p‐Menthyl‐3‐carboxaldehyde as Chiral Auxiliaries

AbstractReview: 70 refs.

Molecular Structure of Hydrazoic Acid with Hydrogen-Bonded Tetramers in Nearly Planar Layers

Hydrazoic acid (HN(3))--potentially explosive, highly toxic, and very hygroscopic--is the simplest covalent azide and contains 97.7 wt % nitrogen. Although its molecular structure was established decades ago, its crystal structure has now been solved by X-ray diffraction for the first time. Molecules of HN(3) are connected to each other by hydrogen bonds in nearly planar layers parallel to (001) with stacking sequence A, B, ... The layer distance, at 2.950(1) Å, is shorter than that in 2H-graphite [3.355(2) Å]. The hydrogen bonds N-H···N are of great interest, since the azido group consists of three homonuclear atoms with identical electronegativity, but different formal charges. These hydrogen bonds are bifurcated into moderate ones with ≈2.0 Å and into weak ones with ≈2.6 Å. The moderate ones build up tetramers (HN(3))(4) in a nearly planar net of eight-membered rings. To the best of our knowledge, such a network of tetramers of a simple molecule is unique.

Reactions of Unsaturated Azides; Part 27:¹ Synthesis of 1,4-Diazidobuta-1,3-dienes

Three different methods to prepare 1,4-diazidobuta-1,3-dienes are presented: nucleophilic substitution of electron-poor dichlorinated substrates, nucleophilic addition of hydrazoic acid at an electron-deficient diallene, and a sequence of prototropic isomerizations of propargyl sulfones followed by nucleophilic additions. In all cases, isolation and assignment of the diastereomeric products was possible, and some sequential reactions, such as reduction or 1,3-dipolar cycloaddition of the azido groups, were performed.

Tautomerism and Thermal Decomposition of Tetrazole: High-Level ab Initio Study

The mutual interconversion and decomposition reactions of four tetrazole isomers (1H-TZ, 2H-TZ, 5H-TZ, and an N-heterocyclic carbene 14H) have been studied theoretically using the W1 high-level procedure. Computations allowed resolution of the existing discrepancies in the mechanism and key intermediates of TZ thermolysis. The tautomeric equilibria between 1H-TZ, 2H-TZ, and 14H turned out to play a very important role in the mechanism of thermal decomposition. Although the barriers of monomolecular tautomeric transformations were found to be high (∼50-70 kcal/mol), the concerted double H atom transfer reactions in the H-bonded complexes of TZ tautomers have profoundly lower barriers (∼18-28 kcal/mol). These reactions lead to fast interconversion between 1H-TZ, 2H-TZ, and 14H. The carbene 14H has never been considered before; however, it was predicted to be a key intermediate in the mechanism of thermal decomposition of TZ. For all species considered, the unimolecular reactions of N(2) elimination were predicted to dominate over the elimination of hydrazoic acid. In agreement with existing experimental data, the effective activation energy of thermolysis was calculated to be 36.2 kcal/mol.

Menthone and p-menthyl-3-carboxaldehyde as chiral auxiliaries

Two chiral auxiliaries and the role they play in the preparation of chiral carbonyl compounds and heterocyclic compounds are presented. Key reactions include S(N)2' displacements, Mitsunobu with hydrazoic acid, and 3,3-sigmatropic rearrangements. One of the auxiliaries serves many functions and is removed either by oxidative cleavage or RCM reaction.

Synthesis of N 1-alkyl-1,4-diazepin-5-ones via Schmidt ring expansion chemistry

Reaction of 4-piperidone with alkyl bromides gave the corresponding N-alkyl-4-piperidones, and treatment of these with hydrazoic acid resulted in the Schmidt reaction to give the corresponding N1-alkyl-1,4-diazepin-5-ones in good overall yields.

ChemInform Abstract: Synthesis of 5‐Substituted 1H‐Tetrazoles from Nitriles and Hydrazoic Acid by Using a Safe and Scalable High‐Temperature Microreactor Approach.

AbstractIn situ generation of HN3 from NaN3 and AcOH in a microreactor coupled to an intensified high‐temperature/high‐pressure flow addition step to nitriles yields tetrazole derivatives in good yields with excellent purities.

Vibrational Spectra and Dynamics of Anions and Acids in Ionic Liquids

Vibrational spectra and energy relaxation lifetimes are reported for the protonated acidic species hydrazoic acid (HN3) and the azide (N3-), thiocyanate (NCS-) and dicyanamide (DCA) anions in imidizolium and phosphonium ionic liquids (ILs). The vibrational spectra and dynamics for the anions in phosphonium tetrafluoroborate and dicyanamide ILs are similar to those previously reported for imidizolium ILs, which resemble the behavior in aprotic molecular solvents such as dimethylsulfoxide. The results are different for hydrazoic acid. In water, methanol and other protic solvents the energy relaxation time is shorter for the azide anion than its protonated and neutral counterpart, hydrazoic acid. In ILs, however, the anion relaxation times are faster than the acid, indicating that the intermolecular interactions are different for acids and anions in ILs compared to conventional molecular solvents.

Copper Azide Confined Inside Templated Carbon Nanotubes

AbstractThe currently used primary explosives, such as lead azide and lead styphnate, present serious health hazards due to the toxicity of lead. There is a need to replace them with equally energetic but safer‐to‐handle and more environmentally friendly materials. Copper azide is more environmentally acceptable, but very sensitive and detonates easily from electrostatic charges during handling. If the highly sensitive copper azide is encapsulated within conducting containers, such as anodic aluminum oxide (AAO)‐templated carbon nanotubes (CNTs), its sensitivity can be tamed. This work describes a technique for confining energetic copper azide within CNTs. ∼5 nm colloidal copper oxide nanoparticles are synthesized and filled into the 200 nm diameter CNTs, produced by template synthesis. The Cu‐O inside the CNTs is reduced in hydrogen to copper, and reacted with hydrazoic acid gas to produce copper azide. Upon initiation, the 60 μm long straight, open‐ended CNTs guide decomposition gases along the tube channel without fracturing the nanotube walls. These novel materials have potential for applications as nano‐detonators and green primary explosives; they also offer new opportunities for understanding the physics of detonation at the nanoscale.

ChemInform Abstract: Regio- and Stereoselective Azidation of 19-Norsteroids.

The proton at C-9 of 3-methoxyestra-1,3,5(10)-trienes 1-4 was replaced by an azido group regio- and stereospecifically in one step by reaction with hydrazoic acid in chloroform in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)

ChemInform Abstract: Selective Deformylation of an α,β-Unsaturated Sugar Aldehyde in a Very Short Synthesis of 3′-Azido-3′-deoxythymidine (AZT) and Its Stereoisomers.

(2E,4S)-5-Acetoxy-4-formyloxy-2-pentenal (2) prepared in one step from tri-O-acetyl-D-glucal was selectively deformylated to give an α,β-unsaturated aldehyde 3 with an unprotected hydroxy group at C-4. Michael-type addition reaction of hydrazoic acid to 3 followed by acylation at C-1 gave a 1:1 mixture of the erythro- and threo-isomers of 5-O-acetyl-3-azido-1-O-(4-biphenylcarbonyl)-2,3-dideoxypentofuranoses 4 and 5. They were used as substrates for nucleoside coupling with silylated thymine to give all four D-isomers of 3'-azido-3'-deoxythymidine 6-9

ChemInform Abstract: An Expedient Synthesis of Diethyl 1-Azidoalkylphosphonates via the Mitsunobu Reaction.

Dielhyl 1-azidoalkylphosphonates were obtained in high yield, and under mild conditions by the reaction of diethyl 1-hydroxyalkyl-phosphonates with hydrazoic acid in the presence of triphenylphosphine/diethyl azodicarboxylate (the Mitsunobu reaction)